Puzzle Bobble 4 continues the gameplay tradition of the previous game in the series, focusing on releasing colored bubbles and matching them to make them disappear. This installment adds new characters to choose from, as well as a Story mode, where the player wins Tarot cards after each completed stage. In Story mode the player sees the story unfold as he defeats each CPU-controlled character (which change depending on the character the player starts with).

The Win Contest mode is a simple "how many games can I win in a row" against the computer. Finally, should the player complete the Challenge mode (where he must complete certain puzzles as fast as possible, and get judged on technique, speed etc.), the Edit mode will become available, which allows players put together their own puzzles, completing with each other.