Two years after the events of Shellshock: Nam 67 in 1969, newly drafted soldier Nathaniel "Nate" Walker is brought to a secret military base in Vietnam by Sgt. Jack Griffin. Jack explains that the army has paid a man named Whiteknight to create a biological weapon to use in the war, but the plane transporting it was shot down. A group of soldiers was sent to retrieve it, but the only member who returned was Nate's brother Caleb "Cal" Walker, who had gone mad. Jack tries to get Nate to talk to Cal and calm him down, but before he can, a group of Viet Cong attacks, and Cal escapes in the confusion. While trying to get away, a Viet Cong captain named Trang corners Nate and attempts to get him to defect and lead him to Whiteknight. Nate and Jack manage to escape, but become separated.
Nate begins to get visions of Cal brutally attacking and killing American troops. When Nate sees a US Soldier get dragged into a tunnel under a church, he jumps in to follow him. On the other side, Nate finds some US troops holding out against the Viet Cong, along with action-obsessed movie star Serena and her cowardly agent Rupert. Nate has his first encounter with an infected, who kills Serena. Nate and Rupert manage to escape on a boat. Nate hears on the radio that Cal has been captured by special forces at a mansion, and the two head that way.