Jewels of Cleopatra 2: Aztec Mysteries is a match-three game with an archaeological theme. Like in the first game, you control Dr. Felicity Turnstone and guide her through each temple level.
Each level is made up of a grid of tiles which the player must match in rows of 3 or more by clicking and dragging tiles, which will clear the tiles and turn them to gold. Felicity Turnstone will follow an automatic path to the exit as the tiles are turned to gold, but the player can right-click on a tile to change her destination. In later levels there are obstacles such as iguanas, armadillos, spiders and scorpions which will block tiles or turn them to stone (requiring more matches to turn to gold) or even send Felicity back to the start of the level. This means that the player has to pick different paths for Felicity to get to the exit of each level.
There are also several types of special objects, triggers, which can turn on lights in dark rooms, move corridors or activate water traps that will make rooms impassable. Again, the player must choose how to move Felicity to reach the right triggers, or escape water traps.
Instead of collecting power-ups and saving them like in the first game, the player has to use power-ups as soon as they are picked up. In addition, there are "treasure" tiles that you can walk on to play a mini-game such as a slot machine game or a tile guess game, but you don't earn any power-ups from these.
Some levels have different mini-games, such as armadillo races which are simple top-down races where you can pick up power-ups to outrun your opponents, and sliding tile puzzles where you have to reassemble a picture. Finally at the end of each chapter there is a level where you must race against a rival treasure hunter to reach the treasure first.