超级病毒“金美拉”和抗生素在运送途中，被恐怖组织头目Sean Ambrose（ Dougray Scott 饰）盗走，Ethan Hunt（Tom Cruise 饰）率领他的IMF小组接受中情局的任务，找回病毒
这次，Ethan Hunt找到了女飞贼Nyah Nordoff-Hall（Thandie Newton 饰）搭档，后者是Sean Ambrose的前女友 Ethan Hunt在获取Nyah信任的同时，二人也暗生情愫
但是，为了完成任务，Ethan Hunt不得不安排Nyah回到Sean Ambrose身边卧底
Nyah终于打探出病毒所在的药厂，接获情报的Ethan Hunt前往药厂准备销毁病毒；另一边，Sean Ambrose已经察觉出了Nyah回到自己身边的真正目的，组织人马在药厂等待Ethan Hunt自投罗网
激烈的搏斗中，Nyah为了帮助Ethan Hunt完成任务，将病毒注入了自己体内，只有在20个小时之内将抗生素注入Nyah体内，才能挽救她的性命，Ethan Hunt又将面临不可能的任务
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