After leading a successful rescue operation of hostages in Mombasa, U.S. Marine Ray Garrison and his wife Gina travel for a holiday at an Italian beachside town in the Amalfi Coast. They are kidnapped by a group of mercenaries led by Martin Axe, who demands to know how the US military learned about the hostages and their location. Ray explains he is not privy to this information and threatens revenge. Axe kills him and Gina.
An amnesiac Ray awakens in the labs of Rising Spirit Tech (RST), a company in Kuala Lumpur specializing in cybernetic enhancements for disabled US military personnel. CEO and lead scientist Dr. Emil Harting tells Ray he is the first successful human subject of the “Bloodshot” program, resurrecting and healing him through the injection of experimental nanite technology now occupying his entire bloodstream. This technology increases his strength and heals his injuries, but the nanites need to be regularly replaced and recharged or he will eventually succumb to damage and die again. When the nanites work at extreme power, they create a red glowing circle of light on Ray’s chest.
Ray is introduced to Dr. Harting’s other patients including former US Navy diver “KT”, with whom he strikes up a friendship, former service member Marcus Tibbs and Jimmy Darlton who overtly dislikes Garrison. After experiencing flashbacks of Gina and Axe, he leaves to avenge Gina’s death. Using the nanites and RST servers to hack into databases, Ray tracks down Axe to Budapest and kills him along with his bodyguards. Back at RST, Ray is put to sleep as his nanites are rebooted. As he has done many times before, Harting then replaces Ray’s memories with a new scenario of how Gina died, this time with Axe’s associate Nick Baris as the culprit. KT objects to Harting repeatedly manipulating Ray’s memories so he will go after different targets without question or remorse, but she is ignored and reminded that RST can kill her by deactivating her enhancements.
Ray awakens, once again amnesiac, and is reintroduced to RST, then experiences flashbacks of Baris kidnapping and killing him and Gina. Driven by revenge, he tracks Baris to East Sussex and kills him, despite the man pleading that RST is lying. Wilfred Wigans, a programmer forced to work for Baris, activates an EMP bomb that incapacitates Ray and severs his link with RST. Ray awakens in Wigans’s office and experiences contradicting memories of who killed Gina. Wigans helps him realize RST has been manipulating him so he would kill the company’s enemies and rivals. Ray tracks down Gina, learning she is still alive but that their relationship ended five years ago and since then she has started a family in London.
Harting sends KT after Wigans. After asking Wigans for help in freeing herself from RST control and taking down the corporation, she tells Harting she failed to capture the programmer. Meanwhile, Ray is recaptured by Dalton and Tibbs and brought back to the laboratory. KT and Wigans sabotage the reprogramming process and destroy the RST computers. Ray awakens and Dalton and Tibbs try to subdue him. After a lengthy battle, he kills them as the RST building is destroyed. Harting confronts Ray, confident that the Marine will surrender now that his nanites have been exhausted. To his surprise, Ray is willing to die to achieve victory and activates an explosive, destroying them both. Ray later awakes with his full memories, revived by Wigans who has updated his technology so his nanites are self-sufficient. The two men and KT then leave in search of a new life.