Guitar Hero: Metallica is the second game in the Guitar Hero series to focus on specific band, following the release of Guitar Hero: Aerosmith.

This title largely borrows from the novelties introduced in Guitar Hero: World Tour, with band career modes for single or multiple players with a storyline drawn as a cartoon, competitive modes online, and the possibility to play with different instruments such as a regular guitar, a bass guitar, drums, and doing the vocals. The storyline describes how a band wants to follow in the footsteps of the Metallica and become a leading act on their tour. This edition adds an Expert+ difficulty mode where players need to drum using a second bass pedal to mimic the playing style of Lars Ulrich, the drummer of the band. The members also did motion capture sessions for the avatars in the game.

The music selection consists of 28 master recordings and 21 additional songs by others selected by the band. Bonus features include various videos and trivia about the songs. Progress is made by completing sets of songs, rather than a series of gigs as in Guitar Hero: World Tour, set in venues that were in important in the band's career. Performances are rated with stars and a certain amount is needed to progress and unlock a new set.

The game also includes the GHTunes from World Tour where new songs can be created and shared. A new Drum Mode offers the possibility to play the drums without an existing drum track to create new rhythms, and the Battle mode (from Guitar Hero III: Legends of Rock), has been updated with Metallica influences for the power-ups, with names like Fade To Black, Under The Ice and Ride The Lightning.

Although released in Europe packaged with a guitar controller and Metallica faceplate, other regions were not so fortunate and only received a solus edition. Custom drumsticks and a second bass pedal were offered as pre-order bonuses in certain stores.

The Metallica tracklist includes:

• All Nightmare Long
• Battery
• Broken, Beat & Scarred
• Creeping Death
• Cyanide
• Disposable Heroes
• Dyers Eve
• Enter Sandman
• Fade to Black
• Fight Fire with Fire
• For Whom the Bell Tolls
• Frantic
• Fuel
• Hit the Lights
• King Nothing
• Master of Puppets
• The Memory Remains
• Mercyful Fate (Medley)
• My Apocalypse
• No Leaf Clover (Live)
• Nothing Else Matters
• One
• Orion
• Sad But True
• Seek & Destroy
• The Shortest Straw
• The Thing That Should Not Be
• The Unforgiven
• Welcome Home (Sanitarium)
• Wherever I May Roam
• Whiplash

The guest tracklist includes:

• Alice in Chains - No Excuses
• Bob Seger and the Silver Bullet Band - Turn the Page (Live)
• Corrosion of Conformity - Albatross
• Diamond Head - Am I Evil?
• Foo Fighters - Stacked Actors
• Judas Priest - Hell Bent for Leather
• Kyuss - Demon Cleaner
• Lynyrd Skynyrd - Tuesday's Gone
• Machine Head - Beautiful Mourning
• Mastodon - Blood and Thunder
• Mercyful Fate - Evil
• Michael Schenker Group - Armed and Ready
• Motörhead - Ace of Spades
• Queen - Stone Cold Crazy
• Samhain - Mother of Mercy
• Slayer - War Ensemble
• Social Distortion - Mommy's Little Monster (Live)
• Suicidal Tendencies - War Inside My Head
• System of a Down - Toxicity
• The Sword - The Black River
• Thin Lizzy - The Boys Are Back in Town

Metallica songs of the Death Magnetic album bought for previous versions are incorporated into the game.