Baron Boris von Frankenstein (voiced by Boris Karloff) achieves his ultimate ambition, the secret of total destruction. Having perfected and tested the formula, he sends out messenger bats to summon all monsters to the Isle of Evil in the Caribbean Sea. The Baron intends to inform them of his discovery and also to reveal his imminent retirement as head of the "Worldwide Organization of Monsters". Besides Frankenstein's Monster (referred to as "Fang") and the Monster's more intelligent mate (voiced by Phyllis Diller) who live in the island castle with Boris, the invites also include Count Dracula, the Mummy, Quasimodo (referred to as "The Hunchback of Notre Dame"), the Werewolf, The Invisible Man, Dr. Jekyll and Mr. Hyde, and the Creature from the Black Lagoon (referred to as the "Creature").
The Baron's beautiful assistant Francesca (voiced by Gale Garnett) enters the lab to confirm that all invitations have been delivered and inquires about one of the addressees named Felix Flanken (voiced by Allen Swift). Frankenstein explains that Flanken is his nephew and successor in the monster business. This displeases Francesca who covets the role for herself. Francesca even asks why there was not an invitation for "It". Boris replies that "It" was not invited since "It" can be a crushing bore, explaining that "It" even crushed the island's wild boars in his bare hands the last time "It" was invited.
Frankenstein has his zombie butler Yetch (Swift impersonating Peter Lorre), Chef Mafia Machiavelli, and the zombie bellhops and servants make preparations for the upcoming party while having some zombies patrol the island to make sure that "It" doesn't show up uninvited. The monsters begin to arrive on the freighter that Felix is also traveling on.
However, when Felix proves to be an incompetent, asthmatic (and unsuitably kind-hearted) human, the monsters plot to eliminate him and gain control of the secret formula. Over time Francesca develops feelings for Felix, after he unknowingly saves her multiple times. As Dracula, Frankenstein's Monster, and the Monster's Mate descend upon Francesca, she sends out a letter (via carrier bat) to an unknown recipient. When the monsters corner Felix upon capturing Francesca, they are frightened at the arrival of "It" (revealed to be a giant gorilla who is a take-off of King Kong) who proceeds to go on a rampage since he was not invited. "It" snatches up the monsters and Francesca (whom "It" develops a crush on).
Felix rushes off to tell his Uncle Boris what happened, and is instructed to head to the boat. Boris leads the zombies in rescuing Francesca from "It" using biplanes. Boris convinces "It" to let Francesca go and to take him instead. "It" complies, releasing Francesca. Felix and Francesca manage to get off the island as Boris and the remainder of the monsters remain in the clutches of "It". Displeased that the monsters tried to steal the secret of total destruction for themselves and attempted to kill Felix as well as having to put up with "It", Boris sacrifices his life by dropping the vial containing the formula, destroying the Isle of Evil and every monster on it.
The destruction is witnessed offshore by Felix and Francesca. Francesca tearfully admits to Felix that she is not human, but is in fact a robot creation of Boris von Frankenstein. Felix answers that "none of us are perfect"âmechanically repeating the words "are perfect", indicating that he has also been a robot creation of his uncle all this time.
Who does Boris rescue from "it"?
Francesca