A secret Department of Defense program called Operation Outcome must be shut down following the public discovery of similar programs and thus its agents, chemically enhanced assassins, must be disposed of. The Bourne Legacy follows Outcome agent Aaron Cross as he escapes assassination at the hands of the organization that created him while struggling with his dependency on the Outcome chemicals that make him what he is.
Following his completion of a harrowing training program in the wilds of Alaska, Cross is targeted by drones sent in by Eric Byer, the CIA official who made the decision to pull the plug on Outcome. Already running low on his chemical enhancement pills, Cross survives the attack and through a combination of cunning and his remaining Outcome resources, makes his way back into the mainland United States in order to find the one person he thinks can help him with his dependency problem.
Cross' potential savior, Dr. Marta Shearing, finds herself in trouble, too, when she is the sole survivor of a an attack orchestrated by Byers to shut down Outcome's research laboratory. Cross arrives in time to rescue her from a second attempt on her life, this time by CIA assassins in her home. The pair make a daring and perilous bid to escape the country and travel to Manila where the chemicals Cross so desperately needs are manufactured.
Over the course of their journey Shearing reveals to Cross that he no longer needs the green pills that physically enhance him, having been infected with the chemical virus in a process called "viraling off" the last time he'd come into the laboratory, rendering the enhancements permanent. He has not been viraled off the blue intelligence pills, however, and Cross makes it clear to Shearing that he absolutely needs these because, without them, he would not posses average human intelligence but would instead barely be able to function.
Byers suspects what the fugitives are trying to do and sends an operative from another super-human enhancement program called LARX to hunt and kill Cross and Shearing. They narrowly escape from the factory after stealing the live viruses that the blue pill are created from and Shearing begins the procedure to viral Cross off, though it will make him sick and render him temporarily useless in fighting off their hunters. Manila police surround the building where Cross and Shearing have been hiding but Cross, now viraled off the intelligence chemicals, escapes and he and Shearing are chased through the streets of Manila by the police and Byers' LARX operative. The film ends with Shearing and Cross, having shaken the police and the operative, taking refuge on a fishing boat leaving the country for Vietnam.