The game is set in a haunted house. Cards are used to represent different rooms of the house, and players explore and react to events that take place in the rooms.
House of Cards requires a token for each player, 2 decks of standard playing cards (jokers optional), and 3 sets of tokens (50 "ghost" tokens, 26 "relic" tokens, and 75 "luck" counters).
One deck is shuffled, with about half the cards (chosen randomly) facing up, then dealt in a grid (the larger the grid, the longer the game). Cards are given relic and ghost tokens based on their suit. The second deck is shuffled normally and hands are dealt to the players.
The player can play cards to collect "luck" counters, move through the house, discovering rooms, collecting relics, and fighting ghosts and other players. Once the target number of relics are collected, the winner is decided.