Dead Rising 2 is set several years after the infamous zombie invasion of Willamette. Unfortunately, the zombie virus was not contained at the conclusion of Dead Rising, spreading unchecked throughout the United States and Dead Rising 2 depicts a country where zombie outbreaks continue to strike.
《丧尸围城2》故事发生在前作5年之后,这时全美国已经被Willamette事件的病毒所感染(剧情中Carlito安排潜伏在全美国的50个携带病毒者爆发)。男主角Chuck Greene,知名的摩托车冠军车手,在一起感染事件中失去了自己的妻子,而仅存的亲人,他的女儿Katey Greene也受到了病毒感染。目前唯一可以控制病情的方法就是定时为女儿注射名叫"Zombrex" 的药剂(1代剧情最后Isabella所研发)。为了获得资金购买药剂,他决定来到Fortune City参加一个名为"Terror is Reality(TIR)"的非人道真人秀节目,到底他们父女会在幸运市有怎样的遭遇?