Following his lab's explosion, Henry and Elizabeth Frankenstein head to London for a rest (and to avoid possible criminal charges). The monster, still alive, follows, but winds up in the Whitechapel district. There, he's mistaken for a disfigured, mentally disabled man and befriended by local prostitutes. When one of the whores is horribly murdered, the creature roams the area, hoping to protect the survivors.

This brings him in contact with the real killer-Jack the Ripper. After 47 years, he's back in action. His 1887 slayings (sacrifices) extended his life. Now he's aging again and desperate to remain alive, and sees in the reanimated corpse of the Frankenstein monster a possible new way to live forever. Henry, the monster and Jack the Ripper's fates become entwined as Jack the Ripper hatches a plan to frame the monster for the killings, to force Henry to reveal his secrets of life and death.