Jennifer Goines takes her power into her own hands in the year 2016 when she forms the Hyenas, a band of crazy compatriots, to take on the 12 Monkeys. With the help of Cole, an elaborate plot is uncovered to reacquire the virus.

With the temporal facility on the verge of destruction, Cole and Jones find themselves in the middle of a coup. After a violent encounter ends in an unexpected tragedy, Cole is sent back to 1957 in a last-ditch effort to save humanity while the rest embark on a caravan across the apocalypse to find Titan -- the stronghold of the Witness.