Eph and Nora finally see their lethal virus in action. Fet takes the security of Red Hook into his own hands while Dutch and Setrakian set off for Staten Island to question Fitzwilliam, Palmer's former body guard.

Eph changes his appearance to leave the city while Nora is left as the reluctant parent for Zack. Dutch and Nora make a deal with Justine to secure Fet's release from jail.

The strigoi are evolving, becoming faster. Smarter. Eph struggles to improve his failing bioweapon while trying to work through the emotional fallout of the abduction of his son, Zack. As Setrakian and Quinlan attempt to crack the Lumen's deepest-held secrets, Fet helps a Navy SEAL team in a deadly mission: search for the Master through the underground tunnels of New York.

The Master’s offer to return Zack plagues Eph as he considers taking the deal. Dutch reunites with an old group of friends but begins to question if her safety is better with them or with Fet, Eph and Setrakian. Palmer strives for answers to Setrakian’s secret strigoi blood treatments and discovers he may have a way to acquire it.

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.

Imprisoned as a subject in a strigoi breeding program, Dutch is desperate to escape and find Setrakian. Gus recruits his cousin for the inside job that will put his gang at the top of the new world’s underground economy, but Creem is suspicious of his business partner’s ambitions.

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.