The Strain, written by Guillermo Del Toro and Chuck Hogan, involves the fall of New York City to a virus that turns its hosts into vampires. The vampire's strain of disease infects people instantly. The virus is brought to New York by way of the Seventh Master, one of the original seven vampire Masters. Eldritch Palmer, a decrepit old man, seeks immortality in exchange for the Master’s conquering of the world.

Those opposing the Master include Ephraim “Eph” Goodweather, his assistant Nora Martinez, rat catcher-turned vampire hunter Vasiliy Fet, and professor-vampire hunter Abraham Setrakian. Setrakian has encountered the rogue Seventh Master decades before. Eph, Setrakian, and the others discover the lair of the Old Master beneath the World Trade Center site. They battle his minions throughout the city, forcing the Old Master to seek out a new hiding place. The three Masters of the New World decide that, if the Rogue Master wants a war, he will get one.