In December 1999, Pierce DuBois, a wealthy angel investor, arrives at Eos Pharmaceuticals in Palo Alto on Christmas Eve. After seven years of funding, David Hume, the Chief Scientific Officer, announces a breakthrough: their compound Eos keeps telomeres (the protective caps on chromosomes that shorten with age) intact through thousands of cellular reproductive cycles. Two injections per year can halt human aging, with sterility as the only side effect. The entire eight-person team has already begun injecting themselves.
Pierce begins calculating enormous profits, but Lisa Perera, the CEO, and David explain why they cannot sell the discovery. Public immortality would trigger overpopulation, environmental collapse, and revolution. Lisa proposes selling Eos to a single buyer: her Stanford roommate Aria Eiffel, the wealthy widow of petroleum magnate Jacques Eiffel, in exchange for dividing Aria's fortune nine ways. Pierce agrees. That same morning, a colleague named Kirsten Besanko died in her pool from an apparent stroke at 33 while six months pregnant, a death Lisa later confesses to having caused. The group, calling themselves the Immortals, resolves to pursue immortality in secret.
Twenty years later, the nine Immortals convene on Aria's private Seven Star Island in the Bahamas. Now in their fifties but appearing as they did in their thirties, they can no longer pass as their legal identities. Pierce and Lisa propose hiring a professional fixer to find physical lookalikes with minimal social ties, eliminate those people, and assume their identities. David objects that this is murder, but the vote passes unanimously. Felix Gentry, the group's CFO, recruits Tory Lago, a Finnish ex-intelligence operative, for the job.
A parallel storyline introduces Zachary Chase, a CIA field agent in London. After completing a dangerous undercover operation involving Ernesto Sargon, a legendary information broker, Chase's superiors order him to falsify his report. Chase refuses on principle, and the CIA fires him.
After his firing, Chase plans to visit his college roommate Lars de Kock, a struggling actor in Venice Beach. Unknown to Chase, Tory has already targeted Lars as a physical match for David. Posing as a CIA recruiter, Tory lured Lars to Virginia with a fake job offer, extracted his biographical details through a bogus interview process, and killed him. When Chase arrives in Los Angeles, he finds Lars's apartment surrendered by an impostor who turns out to be David using Lars's stolen identity. Chase pursues the impostor on a rented Harley-Davidson, but a black Range Rover ambushes him on a cliffside road. He survives a fall of nearly 200 feet thanks to Army Airborne parachute landing techniques but sustains knee and ankle injuries.
Determined to find Lars, Chase stakes out Berret's Taphouse Grill in Virginia, the bar where he last saw his roommate. On the third evening, Tory arrives with his next target: Skylar Fawkes, a former professional triathlete and firefighter whose career-ending smoke inhalation injury has left her with depression. Chase plants a GPS tracker on Tory's rental car and follows both of them. The next day, Tory drives Skylar to a mortuary he presents as a secret CIA facility. Inside, he drugs her and loads her into a cremation retort, a furnace designed to incinerate human remains. Chase infiltrates the building, but Tory ignites the furnace, incapacitates Chase with a blow to the solar plexus, and flees. Chase slams the Emergency Stop button and drags Skylar from the fire. She survives with burn marks across her body but no life-threatening injuries.
Chase explains everything to Skylar, and she vows to help him catch Tory. They deduce that the goal is not murder but identity replacement: Someone who resembles each victim wants to assume their life. Using the FBI's Facial Analysis, Comparison, and Evaluation (FACE) system, they identify several women who resemble Skylar. The strongest match is Sandy Wallace, a chef in Miami. They create a fake Facebook profile to lure Tory there and travel to warn Skylar's lookalikes in person.
Meanwhile, the Immortals are being killed. Eric Curtis, a research scientist in the group, dies in a skydiving accident when his parachute snarls. Camilla Rose, Lisa's executive assistant and an Immortal, is found dead on a patio below a guest balcony. Ries Robins, another research scientist, is murdered while rock climbing when an assailant cuts his rope. Allison D'Angelo, also a research scientist, crashes her car after being drugged through a canister hidden beneath her seat. Felix collapses at a restaurant when his wine is contaminated with a compound that interacts fatally with his heart medication. The terrified survivors cannot identify the killer. Lisa and Pierce, meanwhile, hire strategist Carl Casteel to orchestrate an unprecedented bipartisan run for the White House, seeking political power to protect the group.
Panicked by the mounting deaths, Lisa flees the country on her private jet. She is killed midflight by a batrachotoxin injector, a device loaded with a lethal frog-derived poison, hidden in her seat and triggered by the plane's altimeter. Only three Immortals remain: Pierce, David, and Aria.
In Miami, Chase and Skylar spring their trap. Skylar impersonates Sandy for a chef audition on a yacht Tory has rented. When Tory leans in to watch her cook, she flings a pan of superheated truffle oil into his face, blinding his left eye and severely burning him, then knocks him unconscious. They chain him on their own rented boat and interrogate him. Tory's knowledge proves surprisingly limited: He has nine anonymous clients, communicates only with Felix through encrypted phones, and does not know who his employers are or who is killing them. Chase tries Felix's encrypted phone but gets no answer; Felix is already dead. Using an email tracking service, Chase traces one of the remaining clients to Seven Star Island.
They leave Tory locked in a cremation retort at a Miami funeral home without igniting it, then sail for the Bahamas. On Seven Star Island, Aria has summoned Pierce and David to her fortified estate. Over a lavish feast, David confesses that he is the killer. He explains that the Immortals devolved from brilliant scientists into murderers, stealing innocent lives to preserve their secret while contributing nothing to the world. He killed Eric first, his best friend, so he could never turn back. He reveals that at the last semiannual meeting, he replaced everyone's Eos injection with Astraeus, a compound he invented that destroys telomeres and prevents cellular reproduction. All three, David included, are already dying. He offers a peaceful end: morphine injected while floating in Aria's pool.
When Chase and Skylar arrive and scout the island with a drone, they find three motionless figures in the pool. Approaching on foot, they encounter Tory, who has escaped the crematory, looted Aria's vault, and reached the island independently. Tory attacks, knocking Skylar unconscious with a briefcase. In a brutal fight, Chase exploits Tory's blinded left eye and eventually kills him with a letter opener. Investigating the estate, Chase finds Pierce and David dead in the pool from apparent morphine overdoses. Aria's body lies near her opened vault, where Tory used her dead hand on the palm reader. Chase and Skylar load the vault's remaining cash, gold, and jewels onto their yacht and sail away.
In the epilogue, set six months later, Chase and Skylar are exploring the Caribbean as a couple. No news of the deaths has surfaced because the Immortals had already erased themselves from the grid. They arrive at an unmarked door and knock. Inside, a gray-haired man, implied to be Sargon, the information broker from Chase's London operation, greets them: "So, you need new identities." The story comes full circle, with Chase and Skylar seeking the same kind of disappearance the Immortals once pursued.