Once outside, Sven is almost run over by someone driving Corey's car so Corey and Amy chase the car thief into the woods. Meanwhile, Mei, who gets a call from her twin sister Jun, goes with Sven to rescue her, but fails as Jun is killed by a monster.
The duo finds Corey's car, however its owner gets angry and, along with Amy, kills the now mutated thief. After some more walking they notice a disfigured man, fight some new monsters (Harpies) and walk through the forest to eventually end up in the "Fallcreek University Hospital", where they find Shannon and her brother Kenny, the latter of whom is badly ill due to sniffing the drug made by the black spore flower. He can't find his medicine and eventually succumbs, turning into a monster.
Then the whole group reunites in the hospital's east ground floor, where they make a chemical dynamite to destroy a wall and get to the parking lot. Sven and Corey help everyone to get into a warehouse, but they are surprised by a monstrous Kenny who throws Corey into a pole and kills Mei, greatly distressing Corey. Stan, having responded to Kenny's call before mutating, meets with the surviving group and drives them away, until he crashes off and falls into a dam. Shannon and Stan explore the Dam and the whole group finally reunites to find Amy in a corner of the room.
After locating Amy they find that this was as a result of Kenny's actions, who implied that he raped her. The group escapes, but Corey and Shannon stay and defeat him by making him fall into a pit with a giant metal apparatus falling onto him.
As the game progresses, Stan and Shannon eventually get closer. Whilst 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 to allow Amy to escape.
When they find Sven impaled on a meat hook by the disfigured man at an abandoned house, Stan and Shannon chase after the disfigured man, leading to the ruins of the school from the first game and a tree with huge moving branches. The huge tree was actually the mutated remains of Leonard Friedman (from Obscure) whilst the disfigured man is his son, Jedidiah. Friedman had injected himself with a strain of virus that mutated him which was then passed on to Jedidiah. Stan and Corey kill the Friedman tree, while Corey finishes off Jedidiah, avenging Sven's death.
When the pair return, they find Richard and an ambulance carrying a pregnant Amy. Stan and Corey find out that the fraternity, Delta Theta Gamma, is a Skull & Bones-like organization who want to experiment with Kenny's offspring. The ambulance takes 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 and try to reach it, whilst Corey goes to rescue Amy.
Corey arrives first to see Richard taking off with Amy in a helicopter. But the ride is stopped by a yet living and more powerful Monster Kenny, Corey decides to fight Kenny, but the fight doesn't last as Kenny manages to infect Corey.
When Shannon and Stan reach the new destination point they see Corey, just as he is infected prior to the entry of Stan and Shannon, on his knees. He states that Mei was the only one he cared about, then 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, however Shannon swears that she will not let it live. The helicopter containing Amy and Richard fills up with a cloud of spores before it explodes. Stan asks Shannon what to do next; she replies that she will continue on and cut all family ties.
