In 2003, a sudden Cordyceps virus epidemic swept the world, plunging mankind into an unprecedented crisis.This virus turns infected people into bloodthirsty monsters that attack their own kind mercilessly.In this catastrophe, Joel lost his beloved daughter Sarah, and this scene became an eternal pain in his heart.

Time flies, twenty years have passed, and the raging virus has caused human civilization to almost collapse.Survivors established security quarantine areas in various places, managed by the Federal Disaster Relief Agency (FEDRA).In the Boston quarantine, Joel and his partner Tess relied on smuggling to make ends meet while also looking for their missing brother Tommy.

One day, Joel purchased a batch of car batteries from a gangster, but unexpectedly the batteries were resold by the gang to the underground organization “Firefly”, which was an anti-disaster relief agency.When Joel and Tess went to the gang to pursue them, they found that the gang had been wiped out due to the conflict with the leader of the fireflies, Marlene.The injured Marlene proposed a deal to Joel: As long as they send a 14-year-old girl Ellie safely to the Massachusetts State House, they can exchange any supplies they need.

Although Joel and Tess were dissatisfied with Marlene's request, in order to survive and possibly exchange supplies, they still took Ellie to sneak out of the quarantine area at night.However, their actions were discovered by a patrolling soldier.Ellie takes advantage of the soldier's opportunity to test for viral reactions and stabs the soldier, causing the soldier to prepare to shoot her.Joel did not want the tragedy to happen again, so he beat the soldier to death in anger.

Later, Tess used the soldier's detection equipment to discover that Ellie was actually an infected person.However, Ellie insists she was still alive after being infected with the virus for weeks.In order to avoid the incoming Disaster Relief Agency patrol, the three are forced to cross the urban center classified as a biological and chemical pollution zone.