国际安全局的王尚恩（安志杰 饰）率万飞（周杰伦 饰）等部下远赴约旦，押送制造天花病毒变体的科学家肯纳，岂料王尚恩叛变将肯纳劫走，万飞头部受重伤，他同队中的心上人也在这次任务中身亡。三个月后，王尚恩等人研制的病毒造成一艘货船上的人们尽数死亡，而他此时准备贩卖疫苗谋取暴利；万飞在医院中被告知头部的子弹无法取出，神经受损导致他两周后会有生命危险，万母向其透露他有一个失散多年的哥哥。为了完成母亲心愿，万飞前往吉隆坡寻找哥哥万阳（谢霆锋 饰）。飞机上与万飞同行的简博士恰巧是王尚恩一伙准备用来替换肯纳的病毒专家，简博士被王尚恩派出的万阳劫持，万飞出手相救。因为分属不同阵营，兄弟只得拳脚相见……International Security Affairs agent Jon is on a dangerous mission to escort a criminal scientist to another country. En route, a member of his team, Sean, turns out to be a traitor and shoots Jon in the head while kidnapping the scientist. When Jon wakes up in the hospital, a doctor tells him that within weeks, the bullet in his brain will cause complete paralysis. Jon returns to Beijing to see his mother, who confesses that Jon has a brother in Malaysia who was raised by his father, a gambler. Jon takes a flight to Malaysia to find his brother, Yeung. On the plane he forms a bond with Dr. Kan, who promises to look into possible treatments for his condition. However, when they arrive, Yeung tries to kidnap the doctor and when Jon intervenes, he's also taken hostage. The two soon realize they're brothers, and decide to work together in order to keep the criminals behind the kidnappings from reinfecting the world of a disease long thought cured.