These levels have an unlimited number of lives, so if any single ball reaches the emblem, the player will simply restart the level, since there is no game over in boss levels. The enemies in turn shoot projectiles that will induce a certain gimmick if they hit the player. There are also boss levels where the player has to shoot balls towards the enemies to reduce their hit points while simultaneously preventing the ball string(s) from reaching the skull emblem. Some levels feature two lily pads that the frog can jump between, while other levels set the frog on a horizontal or vertical track and enable it to slide side-to-side or up-and-down rather than rotate to aim. Zuma's Revenge! introduces three types of levels that are new to the series.

These include a visual guide to show where a ball will land when shot, power-ups that slow down or reverse the direction of the string, a three-way cannon that blasts through all layers of balls, a laser that can destroy single balls, a bomb, and a lightning power-up which destroys all balls of a specific color.

Periodically, random balls display power-ups which the player may collect by destroying the ball. The strings are always 'pushed' by the last ball in the string, so any balls not connected to the rearmost string do not move on their own. However, unlike in the original Zuma in which regardless of stage, they are allowed to play stage one of the temple again, when the player gets a game over, they will start again at the checkpoint (stage one of an area if the player loses before the mid-level and stage six if the same situation happens in stages six to ten). Should they reach the emblem, the player gets eaten by the skull emblem and loses a life, and the game ends when the player runs out of lives. The strings of balls constantly roll along their tracks toward a skull emblem at the end. Gaps automatically close if the balls at either end of the gap are (or become) the same color, potentially creating chain reaction matching and clearing as new sets of three or more are formed. This clearing creates gaps through which a player may shoot more balls at nearby strings, target bonus fruit, and 'power-up' stones.

When three or more balls of the same color match together, they are cleared from the playfield. Players move a ball-shooting frog which always points in the direction of the mouse to aim and fire balls at these strings. As in Zuma, the main objective of Zuma's Revenge! is to clear strings of rolling balls, or 'stones', by matching balls of the same color.

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