As the story of a familiar operative draws attention around the globe, another government program, named Operation Outcome, decides to terminate its own agents to conceal its secrets. Aaron Cross, one of Outcome's six agents, is on a training exercise in Alaska, unaware of the program's shutdown. Meanwhile, intelligence operations director Eric Byer, tasked with controlling the fallout, initiates a plan to systematically eliminate all Outcome agents. Cross, expertly trained and heavily medicated to enhance both physical and mental capabilities, survives an assassination attempt and starts to unravel the implications of his existence within the program.

On the run and in need of medication to retain his enhanced abilities, Cross finds an ally in Dr. Marta Shearing, a scientist involved in the Outcome program's genetic alteration processes. After surviving a deadly shooting by a brainwashed co-worker at her laboratory, Shearing's life is thrown into disarray. With no one left to trust, she and Cross form a reluctant partnership. As they seek to escape the tightening grip of the organization that once controlled them, they must outmaneuver Byer's resources and agents, leading to a globe-trotting game of cat and mouse that will test the limits of their skills and determination.