In a round, the active player moves their character to a different location on their board, takes one or more of the actions visible at that spot (often by playing cards from their hand), and then refills their hand to four cards. The cards are allies, items, effects, conditions, and (for some characters) curses. 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 their deck, and then play one of them on their board, covering two of the four action spaces in one of that player's locations. The fate deck contains heroes, items, and effects from the villain's movie, and these cards allow other players to hinder that specific villain.

Villainous: Despicable Plots can be played standalone, but also in combination with any other title in the series.