Dracula, the owner of a lavish hotel for monsters, has opened its doors to human guests now that his daughter Mavis has married a human named Johnny. When Mavis and Johnny have a baby boy named Dennis, Dracula becomes concerned about whether his half-human, half-vampire grandson will exhibit any vampire traits. As Dennis approaches his fifth birthday without showing any signs of being a vampire, Mavis starts considering moving to Johnny’s hometown in California to give Dennis a more typical, human upbringing.

Determined to keep his family together and ensure Dennis embraces his vampire heritage, Dracula enlists his friends Murray the mummy, Wayne the werewolf, Griffin the invisible man, and Frank the monster to help train Dennis in the ways of a young vampire. While Dracula goes to great lengths and misadventures to awaken any latent vampire abilities in his grandson, Mavis experiences culture shock during her visit to California but begins to see its appeal. Meanwhile, unbeknownst to them, Dracula’s father Vlad decides to pay an unexpected visit to the hotel, leading to potential clashes between old-world vampire traditions and Dracula's more modern approaches.