Two weeks have passed since the events of the Hangman Returns. Jericho Caine and Father Tom Padilla, the Death Brothers, return to The Reefs in the Gulf of Mexico to settle a score with the vampire sirens. However, a female angel, Sariel, with romantic intentions toward Jericho, plans to separate the brothers and seduce the slayer. Sariel strikes a deal with the Hangman to distract the brothers by casting a spell that resurrects vanquished supernatural beings in New York. In return, Sariel agrees to help the Hangmen bring back his wife and son, who are in heaven.

Sariel also recruits a vengeful scientist, Dr. Ranken, to create a monster, who is a combination of a rare male vampire siren, and a werewolf. Sariel wants the doctor and his creation, Thaden, to only eliminate Tom, but they have other plans. They hire a hitman to acquire a mystical weapon called the Takara Dagger. It has the power to kill any living being, including angels and demons. They intend to kill anyone that poses a threat to their ascension to power. As the new threat grows, the Death Brothers must face the danger without their allies. Susan Taki, Tom’s girlfriend, is still in a coma in San Diego. The Grand Librarian, Alexander Merryweather, is in Chicago tending to his new family.