Reese tries to catch a flight to Istanbul but computer glitches delay his flight. The gate agent finally gets him a seat in first class on a flight with a stopover in Rome, and asks if he'll need a return ticket. Reese admits that he's not sure if he's coming back. Reese takes the GPS chip out of his cellphone and throws it away. When he boards, the hostess, Holly, asks if he would change seats so that a newlywed couple can be together. Reese agrees and ends up seated next to a talkative older woman. A businessman loudly complains while a child, Titus, plays in the aisle, and Reese asks Holly for a drink.
As the jet takes off, Reese reads an article about the FBI busting an online drug bazaar. When the businessman gives Holly trouble because he refuses to shut off his phone, she appeals to Carlos, who is working coach. He refuses to help and Reese carefully knocks the businessman out when no one is looking, and then takes his cellphone and puts it in his seat pouch. However, once the plane goes to cruising altitude, the businessman's phone rings. He receives a text message simply saying 4C. Reese goes to the back to the plane and discovers that a young man is seated next to a man in a suit. As he goes by, Reese realize that the second man is a Federal marshal and has a gun. Another marshal goes to the front lavatory. By the time Reese gets there, he discovers that the man has been knocked out and someone has taken his gun. Reese pockets his badge and calls Finch.
Finch wonders where Reese is, but Reese figures that his former employer already knows, and deliberately tampered with the computers to get him onto the plane and help a new Number. When he tells Finch what is happening, Finch insists that he has no idea why he is on an eight-hour flight to Rome. He figures that The Machine arranged the whole thing and asks what finch is going to do about the unconscious Marshal. Reese figures that someone is going to kill the young man, who the Marshals are escorting, and tells Finch that he'll warn the first Marshal and then drop the whole thing.
Reese goes back to where the second marshal and his transport are sitting, and tells the marshal what happened to the other man. The marshal tells Reese that it's none of his business, and Reese gets up and stats to leave. However, the marshal clutches at his stomach and passes out. A Colombian man sits down next to Owen and tells him that Raphael sends his regards, and then injects him in the leg with a syringe. Reese doubles back and knocks the man out, and then removes the syringe. He checks the Colombian's ID and discovers that he has a Lanceros tattoo.
Holly notices what is going over and comes over to investigate, and Reese suggests that the two unconscious men are dehydrates. When she goes to get them blankets, Reese tells Owen that the Colombian injected him with a coagulant to give him a pulmonary embolism, and tells him to drink some wine to thin his blood. He then sends a photo of Owen to Finch, who confirms that Owen works for the company that hosted the site where the online drug bazaar was held. The mastermind behind the operation is an individual known only as The Sphinx. Owen claims that he knows nothing about the drug bazaar and that the marshals burst in and arrested him, but Reese figures he knows more than he's saying.
Finch takes Bear and meets Sam in the park, and explains what is happening with Reese. He asks her to visit the ISA and find out what they know about Owen, and Sam realizes that Finch believes that Owen is a relevant. Finch admits that it's possible and that he needs to know why The Machine sent Reese to help Owen.
When he returns to the library, Finch calls Reese, who works out that Owen is a relevant. He accuses Finch of hiding information just like The Machine did and hangs up, and then questions Owen. Reese realizes that the programmer has a stun belt on and takes the remote, and then uses it to force Owen to answer his question. Owen admits that he actually built the drug bazaar and met with The Sphinx personally, and Reese figures The Sphinx wants Owen dead because he can identify him. Finch calls Reese and tells him that the Lanceros is working for Raphael Hernandez, a Colombian drug lord. They figure that Owen can identify The Sphinx and his accounts, and that would lead the feds back to Raphael.
Reese finds Holly in the hostess station and gets a glass of wine. She admits that she's worried about the two unconscious men and Reese uses the stolen ID from the first marshal to pass himself off as a member of the International Homeland Security Department. As he talks with Holly, Reese pockets a corkscrew. He gives the hostess the remote on the stun belt and tells her to push it and signal him if she sees anything suspicious.
Reese checks the plane and spots the newlyweds from earlier. They go to the back of the plane toward Owen and attacks him, and Reese takes them out, shoving them into the hostess station. He pins the man to the wall with the corkscrew while the woman stabs him in the shoulder with a fork. Before Reese can deal with her, Holly knocks the woman out with a pitcher.
Sam goes to a travel agency and greets the clerk, Foster. He pretends that he doesn't know who she is, but Sam points out that the agency is an ISA safehouse. Foster uses the fake agency to make travel arrangements for ISA agents, including the plane that took Sam and her dead partner Cole to Berlin on the final mission. Sam figures that Foster set up Owens' travel arrangements, grabs him, and chokes him until he talks. Foster admits that he doesn't know why Owen is a relevant. However, he did arrange for another ISA operative--Sam's successor--to board the plane.
Reese dumps the two unconscious kills in the lavatory and locks the door. Carlos comes back and Holly gets him to leave, and then bandages Reese's wounds. Finch calls and Reese tells him that the two new killers are ex-Mossad, hired by an Israeli drug lord who doesn't competition from The Sphinx. Sam gets on the line and tells Reese what she's learned, and Reese spots the ISA operative as he heads for Owen with a plastic bag. The man starts suffocating Owen and Reese quickly knocks him out. When the young boy notices what's going on, Reese has Holly give the child a sippy cup filled with whisky to keep him quiet. However, when Reese turns back to Owen, he discovers that the programmer has managed to remove his stun belt and slip away.
Holly calls the captain and explains that they have to divert, but he tells her that there is nowhere they can land. Reese gives the increasingly nervous hostess a drink to calm her down, and Holly complains about all the lousy people on the plane. He assures Holly that she's good at her job just as they hear Owen sneeze. He's hidden in a closet and Reese has enough and knocks him out. Holly wonders what Reese's job really is, and he simply says that he quit. He then asks Holly to open the door to the cargo hold.
Sam dresses up as a waitress at the restaurant where Hersh is eating. When Finch calls to ask what she's doing, Sam tells him that she's meeting with an old friend.
Owen wakes up in the cargo hold and discovers that he has the stun belt on again. Reese is searching for any kind of improvised weapon in the passenger suitcases. He calls Finch who updates him on the flight plan, and they realize that Owen actually is The Sphinx. Owen admits that he is and offers Reese $50 million bitcoins to get him safely off the plane. Disgusted with Owen and Finch, Reese berates the programmer about how they build something and refuse to accept responsibility when it backfires. Owen realizes that he's not talking about just him, while Finch listen silently. Reese is cut off when the ISA operative escapes from where Reese tied him up and enters the cargo hold.
Once she's served him his food, Sam sits down next to Hersh and tells him that she poisoned his meal with scopolamine, rendering him docile and causing amnesia. She demands to know who Owen is and Hersh explains that they set Owen up as The Sphinx in return of 30% of his profits, which they use to help finance the ISA. Since Owen is going public, Hersh's superiors figure he'll expose the ISA to the world, ruining their organization. As Sam goes, the dazed Hersh asks if her current employers are treating her okay. Sam says that they haven't tried to kill her yet and notes that she could have easily killed Hersh if she wants him dead... and that it's a shame he won't remember she spared his life.
Reese and the ISA operative fight it out using improvised weapons from the luggage. Owen finally knocks the operative out with a golf club and Finch calls to pass on what Sam has learned. He's also checked on Raphael and discovered that he once had an entire hotel floor blown up to kill a witness against him. Finch has hacked Raphael's email and discovered that he hired a team of two men to come aboard the plane. However, Finch insists that there's no second Colombian on the passenger list. Thinking it over, Reese realizes that the second killer isn't one of the passengers.
Carlos lures the captain out of the cockpit by bringing food, and then shoots him in the stomach using a pillow as a muffler. After putting on a parachute, Carlos disables the co-pilot, closes the cockpit door, and then puts the jet into a dive toward the Rome airport.
Reese finds the injured captain and does what he can for him, while Holly confirms with the passengers that they saw Carlos enter the cockpit. Finch assesses the onboard flight system and warns Reese that Carlos is flying on manual. When he warns Reese that he's never flown a jet, Reese tells him that he's going to have to.
As the plane starts to angle downward, Reese uses a food cart as a battering ram to break into the cockpit. As he and Carlos fight, Finch grabs a flight controller and hacks into the flight system, trying to bring the plane in safely. Reese knocks out Carlos with a fire extinguisher and Finch brings the plane down for a bumpy but safe landing.
As the passengers disembark, Holly asks Reese what he really does. All he will say is that he helps people, and Holly asks him to help her get a drink later. Once everyone is off the plane, Reese goes to the terminal to pick up a large trunk... and dumps Owen out. He gives Owen the address of a safehouse in Rome and tells him that Finch will set him up with a new cove identity. Owen makes another offer to pay Reese and Reese refuses, and Owen figures that his job is helping people.
The next day, Reese and Holly say goodbye to each other and she gives him his number to call her. Reese spots Finch sitting at a nearby sidewalk café and goes over to join him. Finch admits that he set up The Machine to only give out numbers so that humans would still make the final decision of who should be saved and who shouldn't. He admits that they have great responsibility and free will... and sometimes they suffer great loss. Finch tells Reese that he also misses Carter, and then says that he's going to a museum to see a painting that Grace liked. He invites Reese along and Reese says that he'll be busy... getting a new suit. Reese then asks if he can get a ride back to New York City on Finch's private jet, and Finch gladly agrees.