Tutankhamun features gameplay familiar from earlier versions of this game design, while adding new Egyptian god powers and implementing a modified scoring system.

To set up, shuffle the artifact and god idol tiles, then arrange them in a snake-like pattern that emulates the winding of the river Nile. Players start at one end of the line, taking turns choosing any tile from in front of them along the Nile while never being able to claim a tile they have already passed. Multiple sets of scoring tiles (three sets each of 8, 6, 4, and 2 points), along with ten 1-point scarab ring tiles, can be claimed, and when the last tile of any set has been claimed, the player holding the most tiles from that set scores the number of points listed, while the player holding the secondmost tiles scores half that amount. Whoever has the most scarab tiles when the last one is collected scores 5 bonus points.

Tutankhamun includes two copies each of five different Egyptian god idol tiles. When you collect one of these, you immediately trigger its ability to manipulate tiles on the path, tiles in player's collections, tiles in the Underworld (i.e., the collection of bypassed tiles), or scarab ring tiles in your collection.

When a player reaches zero on the score track at the end of their turn, the game ends and that player will be proclaimed the new High Priest of Egypt!