Guitar Hero: World Tour is the fourth main game in the series and brings a major change to the concept. Following the release of Rock Band that built on the Guitar Hero concept but added additional instruments, World Tour introduces these as well to allow players to play together simultaneously as a real band. Next to the guitar that was the main peripheral for the previous titles, the bundled edition of the game adds a microphone for the vocal parts and drums for percussion. Just like the previous game, the guitar tracks are split up for the lead and bass. The lyrics and the vocal pitch is shown near the top of the screen, while the bottom part is split up for bass guitar, lead guitar and drums, each with a separate set of notes that need to be hit to correctly play the part.

While playing, a rock meter keeps track of successive notes hit (one for each player), which leads to score multipliers. When the meter becomes too low, other players can make up for this on a shared, general performance meter. In the same vein players share a star power meter, built up by playing through certain sections successfully, that any player can access.

There are four difficulty levels and a new beginner mode where notes are made as easy as possible to introduce the concept to new players. Most of the game content is centered around a Career mode (both Solo and Band) where players start a new band, choose an avatar an instrument, and then play different gigs unlocking new songs along the way. Completing tracks earns money that can be spent on outfits or instruments. There are once again encore songs and "boss challenges" where the lead guitar enters a duel. This is similar to the battles in Guitar Hero III, but without the power-ups. Instead it returns to a call-and-response mechanic similar to the Face-Off mode. Bands consists of offline players but online members can join as well. Complete bands can take on others online through the Battle of the Bands mode.

Through the Music Studio editor new songs can be composed and shared using the GHTunes service (not for the PS2). In this edition avatars can be customized with more detail using the Create-a-Rocker mode. Major artists have licensed their appearance in the game. The Wii version contains a Mii Freestyle mode where players can use their Mii characters in-game and compose songs through motions of the Wii remote and the Nunchuk controller.

There are several bundles for the game, based on the amount of instruments included, but also a stand-alone version as most of the versions are compatible with the controllers of previous games and even some of Rock Band.