In Tomes of Arkham each player is a Rare Tomes book collector in H. P. Lovecraft's town of Arkham. Each round players utilise different events in order to acquire the most Renowned Tomes collection. When a player acquires their 8th Tome then everyone calculates their Renown Points, the player with the highest Renown is the winner.

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Players have a number of Resources that they can use to purchase Tomes from the common sale area. Each Tome is part of a larger collection which adds to the Renown that the owner gains at the end of the game. At the start of each round new Tomes are placed up for sale and the First Player chooses an Event card to play later in the round secretly, then passes them to the next player who chooses their event card for the round and so on.

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The Events determine the player turn order and each includes a special ability that the player can use when it is their turn; Henry Armitage can prevent other Events playing, Creative Banking lets players steal resources from other players, Viewing lets players gain resources from the Lost Tomes Collection, Guard Dogs prevent a players Tomes being stolen, Wise Investments allow players to gain Resources, Collector allows players to acquire more than 1 Tome per Round, Wilbur Whateley allows players to steal Tomes and the Stars are Right makes acquiring Tomes cheaper. But players must beware, owning certain Tomes can lead to players becoming Unstable and unlocking bizarre game twisting actions such as swapping Tomes, moving the First Player and losing resources.