Still reeling from the death of President Glass, Deputy Marshal Mason Raines finds himself working for the New Colony. Using his unique skills as both lawman and soldier, he leads an elite team tasked with retrieving critical supplies for mankind's last survivors. While delivering goods to an independent food supplier, known only as "The Farm", Mason uncovers a secret that goes against all that it means to be human. Refusing to join their ranks, he soon finds himself the target of a man willing to do anything to keep that secret from being revealed.

Hundreds of miles away, Tanner and Samantha investigate a cryptic call from the Watts Bar Nuclear Facility. There they discover a menace so great that it threatens to leave the surrounding area forever uninhabitable. When Tanner is captured by a militia group, Samantha is faced with not only surviving on her own, but also finding a way to secure his escape.

With Tanner and Samantha away, Issa secretly departs for Mount Weather to share the exciting news of her pregnancy. Armed with an elephant rifle and her two trusty blades, she discovers a band of men trafficking in those who have been afflicted with the virus. It is then that Issa must decide where her loyalties lie, as well as how much risk she and her unborn child can endure.