Neopets Puzzle Adventure for Wii is a puzzle game where the battles take the form of a game of Reversi. You and your opponent take turns placing tokens on the board, capturing each other's tokens by surrounding them with your own. You can capture your opponent's tokens in several ways: you can place your tokens on either side of a straight line of your opponent's tokens to surround it, or you can win if your opponent doesn't have any tokens left after three moves. The game also features stats and equipment that can affect the outcome of battles.
Outside of battle, you can take on quests, talk to people, fight and capture petpets, and shop for items and equipment. The game's RPG elements allow you to manipulate point totals and do otherwise illegal moves a limited number of times in each battle.
The story follows your journey as you help the crew of the Cyodrake's Gaze when their city is attacked, leading you to find an amulet that becomes a crucial part of your quest. With multiple paths to explore, you must figure out what the amulet does and who's after it before time runs out.