In Villainous - Monstrueusement Malsains, each player takes control of one of three Disney characters, each a villain from a different Disney film: Lady Tremaine (Cinderella), the Horned King (The Black Cauldron), and Gaston (Beauty and the Beast). Each player has their own villain deck, fate deck, player board, and 3D figure.

On a turn, the active player moves their figure to another location on their player board, performs one or more of the visible actions on that space (often by playing cards from their hand), and then draws back up to four cards. The cards consist of allies, items, effects, and conditions. You must use your cards to fulfill your unique win condition.

One of the actions allows you to choose another player, draw two cards from that player's fate deck, and then play one of them on their board to occupy two of the four action spaces at one of their locations. The fate deck contains heroes, items, and effects from the villain's film, and these cards enable other players to confront that villain.

Villainous - Monstrueusement Malsains can be played solo, and the characters can also compete against those from other Disney Villainous games.