It's August 1957, four years after the conclusion of the event of Resistance 2 which left Lieutenant Nathan Hale dead on the battlefield against the invading Chimeran race and Joseph Capelli dishonorably discharged from the U.S. Army for killing Hale. With the Chimera completely occupying the planet, Capelli has given up on the seemingly hopeless fight and has retreated into hiding underground with his wife and young son in Haven, Oklahoma. But as the climate of the planet continues to collapse, scientist Dr. Fyodor Malikov finds Capelli with a plan to deliver a devastating blow against the occupying Chimeran force. In order to protect his family, Capelli must leave them behind and embark on a harrowing mission across the country to New York City. Along the way, he and Malikov will encounter the survivors and remnants left in the aftermath of the brutal Chimeran invasion.