Fet strikes hard at the heart of the strigoi army while Justine embarks upon a risky mission to drive the strigoi out of Manhattan once and for all. Gus and Angel fight for their lives and their freedom but are faced with a moral dilemma.

NYC is falling. Eph and Dutch frantically race to finish their new device to stop the Master before the city is overrun. Justine, Gus, and Angel fight in one last stand to stop the spreading virus. Palmer extracts vengeance for past wrongs but may have crossed the line.

Humanity teeters on the edge of destruction. The Master finally reveals himself, initiating the end game of a battle in which there can be only one winner. Eph, Fet, Setrakian, and Dutch must overcome their personal differences in a last-ditch effort to vanquish the strain.

Out of the ashes of humanity’s nuclear war, Night Eternal has begun. Haunted by the atrocities committed by his son, Eph abandons NYC for Philadelphia. His solitude is cut short when he encounters new fighters who rekindle his drive to fight back. Tasked by Setrakian, Fet and Quinlan search for a new means of stopping the Master.

Quinlan and Fet discover that stealing a nuclear warhead isn’t easy when they encounter an unexpected enemy. Eph and Alex concoct a new weapon to use against the strigoi. Frustrated with his seclusion, Zack discovers a love interest.

Fet and Quinlan track a convoy carrying their prized nuclear weapon; Eph and Alex search for clues to uncover the Master's plan for the fate of the human race; a familiar enemy traps Dutch, who encounters an old friend as well.

Fet and Quinlan must figure out how to get the nuclear bomb back to New York, while a desperate Eichhorst draws near; love-struck Zack tries to learn more about his new crush, but makes a devastating discovery.

With his health failing, Setrakian ignores Eph's warnings and pushes himself to the limit in his quest for victory and revenge; Fet and Quinlan race back to Manhattan, while the Master seals off the city and prepares to eliminate them all.

Reeling from loss, the heroes regroup; the heroes devise a new plan to track the Master through human collaborators, beginning at the blood farm with someone Dutch knows all too well.

An unexpected guest brings old conflicts to the surface, dividing the heroes and threatening the group's trust; with questionable new intelligence in hand, the group launches a make-or-break final assault on the Master.

In the series finale, Quinlan devises a desperate plan, but the costs are enormous. Eph wrestles with his conscience, Fet undertakes a suicide mission, and Dutch and Gus dig in for battle as humankind makes its final stand against the Master and his Strain.