As the story begins, a new drug created from a strange flower is quickly spreading its influence over the University's populace. Soon enough, a small group of students along with the Leafmore High survivors have to face a horde of mutants and stop the spread of contagion before the situation becomes critical.
The students meet a scientist, Richard James, who is immersed in the biology of the scientific black spores, and aids the player several times.
The spores spread through the campus and affects the nearby hospital. Mei, who gets a call from her twin sister Jun, goes with Sven to rescue her, but fails when she is killed by an unknown monster. The player eventually switches to Corey, and he finds Shannon and her brother Kenny, who is badly injured by the black spores and turns into a monster.
When Sven and Corey meet up at a warehouse with the others, monstrous Kenny appears and kills Mei, thus distressing Corey. Stan having respond Shannon's call and meets with the surviving group and drives them away, until he crashes off a cliff into a forest. Eventually, Kenny strikes again, while Corey and Shannon defeat him by making him fall into a pit in a warehouse.
As the game progresses, Stan and Shannon get closer. While they find a place to take refuge, Amy and Sven explore and are ambushed by a man with a disfigured face carrying a chainsaw. The disfigured man fights Sven while Amy escapes.
When they find Sven impaled on a meat hook by the disfigured man at an abandoned house, Stan andShannon chase after the disfigured man, leading to the ruins of the school from the first game, to find a tree with huge moving branches. The huge tree was actually the mutated remains of Leonard Friedman (fromObscure) and the disfigured man is his son, Jedidiah. Friedman had injected himself with a strain of virus that mutated him and was passed on to Jedidiah. Stan and Corey kill the Friedman tree, while Corey finishes off Jedidiah.
When the pair return, they find Richard James and an ambulance carrying a pregnant Amy. Stan and Corey find out that she was raped by Kenny. The ambulances take Stan, Shannon, Amy, and Corey away, but they crash at a bridge after going through a cloud of spores. Stan and Shannon try to find out where Richard's new pick up point is, to try and reach it, while Corey goes to rescue Amy.
When Shannon and Stan reach the new destination point, they find Corey fighting Kenny, and Richard James taking off with Amy in a helicopter. Corey, feeling desolate, states that Mei was the only one he cared about, and commits suicide. Stan and Shannon kill Kenny by crushing him with a huge platform of lights over the football pitch.
As Kenny lies dying under the platform, he pleads to Shannon to take care of his child. Shannon swears that she will not let it live. The helicopter containing Amy and Richard fills up with a cloud of spores, and the helicopter explodes. Stan asks Shannon what to do next. She replies that she will continue and cut all family ties.
