Combat revisions have been made: now the player can stock up to four weapons at once with the help of two sets of load outs that can be interchanged at all times.

There are five new weapons in the game, including a large syringe dubbed The Painkiller and an oversized pair of scissors titled The Guillotine. Co-op has also been fully integrated into the story-mode allowing for an exclusive campaign. The biggest addition is a new playable character, Yuki, who controls differently from The Dishwasher in combat. Recurring elements from the original include Dish Magic and Shop Bots where one can buy upgrades and items with money received through defeating enemies. The game is a side-scrolling beat 'em up where the player must violently dispense of enemies with the help of numerous weapons. Gameplay remains largely similar to that of its predecessor. The game was showcased at the PAX East 2010 convention. The main story revolves around The Dishwasher's quest for universal freedom and Yuki's quest for revenge against the three marks of power that robbed her of her life. Players assume the roles of The Dishwasher and his stepsister Yuki, in two separate solo campaigns, as they battle through legions of enemies and try to unravel the secrets of their pasts. It is the sequel to The Dishwasher: Dead Samurai, also by Ska Studios, released in 2009. It was developed by Ska Studios and released for the Xbox 360 via XBLA on April 6, 2011, and for the Microsoft Windows, Linux and macOS on via Steam. The Dishwasher: Vampire Smile is a 2D side-scrolling beat 'em up video game.

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