For trying to replicate Dr. Frankenstein's experiments, Dr. Gustav Niemann [Boris Karloff] is imprisoned, where he meets another incarcerated criminal, the hunchback Daniel [J. Carrol Naish]. Niemann promises to craft a new, beautiful body for Daniel and wins him as an assistant. During an earthquake, the two escape and stumble upon a traveling showman, Professor Bruno Lampini [George Zucco], whom they murder to seize his horror exhibit, which notably contains the recovered corpse of Count Dracula. To exact revenge on Burgomaster Hussman [Sig Ruman] for imprisoning him, Niemann revives Dracula. Dracula hypnotizes Hussman’s granddaughter-in-law Rita Hussman [Anne Gwynne] and kills the Burgomaster. Hussman’s grandson notices the carnage and alerts the police, who close in on Dracula. Waiting in a nearby carriage, Niemann realizes the police are pursuing Dracula, and he jettisons Dracula's coffin so he can flee with Daniel. As Dracula scrambles to reclaim his coffin, the sun rises and destroys him.
Niemann and Daniel press on to the flooded ruins of Castle Frankenstein in Visaria. Along the way, Daniel saves a Romani woman named Ilonka [Elena Verdugo] from being whipped by a partner over money, and he becomes smitten, convincing Ilonka to join their journey. At the castle, they discover the frozen cavern beneath the ruins holds the bodies of Frankenstein's monster [Glenn Strange] and Larry Talbot [Lon Chaney Jr.], who are thawed by Niemann. Talbot returns to human form, and Niemann vows to cure his werewolf curse by transferring his brain into a different body if Talbot helps locate Frankenstein's notes. Seeing that Ilonka has fallen for Talbot, Daniel proposes that Niemann transfer his brain into Talbot's body instead. Talbot indeed finds the notes, but Niemann’s real interest shifts toward reviving the monster and extracting revenge on two former associates rather than honoring any promise to Talbot or Daniel.
That night, Talbot experiences another transformation into a werewolf and murders a villager, sending the town into a panic. Ilonka warns him that he is a werewolf, but she remains determined to help. Not trusting Niemann to cure him, Talbot instructs Ilonka to fashion silver bullets and wait in his room with a loaded gun. When the moon rises, Niemann succeeds in reviving the monster, and Talbot again becomes the werewolf. The Wolf Man attacks, fatally wounding Ilonka before she dies. Daniel blames Niemann for Ilonka’s death, arguing that Nero’s plan would have kept her safe if Daniel’s brain had been transferred as requested. In a dramatic turn, the monster intervenes, hurls Daniel out a window, and, with Daniel dead, drags the nearly unconscious Niemann outside. The villagers pursue them into the marshes, where the monster and Niemann drown in quicksand.
