Ten years after the animals were cured but at the cost of sterilizing the human population, a new threat rises in the form of "the hybrids," an army of unstoppable lab-made creatures focused on destroying mankind.
Jackson and Logan discover a link between the hybrid attacks that occur in Portland and New York; Mitch is interrogated by a woman claiming to be his daughter, Clementine; and a new development in Abraham's research into the sterility crisis endangers his family.
Abe and Dariela ponder over making a deal that will betray their friends. Abigail's game of cat and mouse continues. Clementine's past catches up to her.
While Jamie's under arrest, she manages to manipulate Mitch and Logan into helping her hunt shepherds, members of a secretive group responsible for sterilizing humans.
Abigail holds Jackson prisoner in order to extract information from him that is critical to her secret master plan, and the team faces a mid-air crisis when their plane experiences an electrical malfunction.
Logan tries to destroy the hybrid nests before they activate. Clem's pregnancy undergoes a surprising development. The team tries to perfect the cure using Abigail and the hybrids.