A policeman, who is fearless to death, can do anything for just one truth, while a gangster, who fears death the most, has drew life threats from his risky action all for love. One policeman and one gangster can be great partners that you have never imagined. Somehow, rescue of the world now is entirely relying on the partners. Within 36 hours, they must resolve the crisis that could destroy the Harbor City...

重案组刑警吴英雄（赵又廷 饰）在拯救客机后成为警界明星，出演各种警队宣传片风光无两。是日，海港城陷入突然危机，高铁、跨海大桥等交通要道突发连环爆炸，吴英雄在追索嫌凶过程中与东区分局刑事侦查组刑警陈真（林更新 饰）结为搭档，又再度重逢被逼做人肉炸弹的通缉犯徐达夫（黄渤 饰）。原来，一号为“夜行者”的神秘组织绑架了徐达夫等通缉犯的家属，逼迫他们作为人肉炸弹将海港城通向外界的各通路炸毁，使海港城变为孤城，以释放生化病毒，执行毁灭城市的“枯草计划”。吴英雄和陈真为解救徐达夫妻子杜小晴（关颖 饰）并阻止枯草计划，与鉴识官蓝西英（张钧甯 饰）、黑鹰队成员黄世楷（修杰楷 饰）等人向夜行者发起挑战。