Guns, Gore & Cannoli is a 2D side-scrolling shooter set during the 1920s Prohibition in the United States. The game follows Vinnie Cannoli, an enforcer for the mob, as he travels to Thugtown to retrieve Frankie on behalf of his boss Belluccio. However, upon arrival, he discovers that something is amiss in the town, which has been taken over by rioters who turn out to be zombies. As Vinnie navigates through the side-scrolling environments, he must fight against gangsters and zombies while uncovering a deeper mystery.
Vinnie's gameplay involves moving through levels, taking out enemies with a variety of guns and melee attacks. He can duck, jump, and use small platform elements to navigate the environment. The game features a range of guns, including pistols, shotguns, flamethrowers, and Tesla coils, each with limited ammo that must be replenished by eating Cannoli. Vinnie can also throw grenades and Molotov cocktails to take out groups of enemies. Enemies come in different varieties, such as zombies, giant butchers, and flying creatures, and require strategy to defeat.
The game supports local multiplayer matches for up to four players on the same screen, with options for AI-controlled bots and custom settings. The main story campaign can be played cooperatively with two players, offering a unique experience.