Another day in the city of Townsville, and this time, the Powerpuff Girls are off on a scavenger hunt! Ms. Keene has given the girls a list of different items that can be found in the city. Along the way, Blossom, Bubbles and Buttercup will run into familiar villains such as Mojo Jojo, Fuzzy Lumpkins, The Gangreen Gang, the Boogie Man, and of course... HIM.

Him and Seek is a side-scrolling adventure game starring the Powerpuff Girls. There's no platforming required in this game, as the girls can fly everywhere. Instead, it plays like a combination of a beat-em-up and a point and click adventure game. The girls will need to perform tasks for Townsville citizens to get items for their scavenger hunt list, ranging from destroying crazy monsters, to finding lost wallets, to beating up the Gangreen Gang to get a tooth!

Initially, you can only control one girl at a time, attacking with punches and kicks, shooting laser beams, and dashing. However, later the girls decide to team up, and you can switch girls on the fly by pressing the L Button. There are also some cool mini-games, such as an excellent pinball machine, a Dance Dance Revolution-like dance-off against the Boogie Man, and a Frogger parody where you control Mojo Jojo as you help him escape from jail and avoid capture by the Powerpuff Girls.