杰森·伯恩事件引起连锁反应，踏脚石（Treadstone）计划以及CIA用药物控制强化特工的行径通过报纸公之于众，令其幕后人物坐立不安。为了阻止满盘皆输的局面出现，CIA高层决定中止该计划，并将相关特工人员以及科学家从行动中抹杀。在此后的日子里，那些深藏在国家政治最底层、依靠蓝绿药丸执行各种绝密任务的特工相继殒命，而负责染脏双手的执行人——前美国空军上校艾瑞克·贝尔（爱德华·诺顿 Edward Norton 饰），正慢慢将屠刀伸向隐藏在位于阿拉斯加崇山峻岭、暴雪深山中的特工艾伦·克劳斯（杰瑞米·雷纳 Jeremy Renner 饰）。 　　突如其来的炮火袭击令艾伦意识到自己所处的危险境地，在之后的日子里，他不仅要在昔日同伴的追杀中求生，还必须设法找到那曾为他提供源源不断体能和智力的蓝绿药丸……The events in this movie take place around the same time as the events in The Bourne Ultimatum (2007). When a British reporter was writing an expose about Black Ops operations Treadstone and Black Briar, and the ones responsible for them are concerned. And when Jason Bourne, former Treadstone operative got the file on Treadstone and Black Briar and gave it to Pamela Landy who then passed it to the media. When the men behind Treadstone and Black Briar learn of this, they're concerned how this will affect other ops they have. They decide it's best to shut down all ops and make sure make everyone involved disappears. They try to take out Aaron Cross who is part of another op called Outcome, but he manages to survive. He then seeks out Dr. Marta Shearing who worked on him when he began. It seems part of the program is for all subjects to take medications but he has run out, which is why he seeks her. But someone tries to kill her. He saves her and she tells him, he should have stopped taking the medications long ago. They go to Manila so that she can help him. Later the men behind Outcome learn that Cross and Shearing are still alive. They try to get them.