Spot it! Party features a deck of Spot it! cards with symbols that differ from those in the original game or any previously released version: a gnome, a plunger, headphones, and so on. Each card in Spot it! features eight different symbols, with the symbols varying in size from one card to the next; any two cards have exactly one symbol in common. For the basic Spot it! game, reveal one card, then another. Whoever spots the symbol in common on both cards claims the first card, then another card is revealed for players to search, and so on. Whoever has collected the most cards when the 55-card deck runs out wins.
To this basic game Spot it! Party adds eight colored card holders and (more importantly for gameplay) a "hand mascot" – a totem shaped like the eyeball-bearing hand in the game's logo. Six new mini-games – such as called "The Race", "Dynamite", and "Double Frenzy" – incorporate the card holders and hand mascot into the gameplay. In "The Tower", for example, players still need to make matches, but they also need to keep an eye out for opportunities to steal or pass the hand mascot in order to have a chance to win.