In the sequel to the PSP-exclusive Medal of Honor: Heroes, players take the role of OSS Operative John Berg during the Normandy campaign of June 1944 in eight missions. He needs to get behind enemy lines and prevent Hitler from deploying the V2 rocket, with the help of US troopers. The story is told through briefings with still voices and narrated voice-overs.

Next to the classic first-person shooting gameplay true to the series, the Wii version offers a new, more accessible mode with on-rails shooting - the computer handles the movement while players only need to aim and shoot. In the regular mode, players move around with the analog stick, look around with the Wii remote, lean with the Nunchuk and fire with the B-button, a departure from the control system introduced in Medal of Honor: Vanguard. The game also offers a lock-on system with the Z-button. Alternately, players can use the Wii Zapper to aim and shoot.

The regular combat remains, but much more events have been added with a few mini-games thrown in. For instance, players need to twist the Wii remote to tune a radio for mid-game incoming information and the sound comes through the remote's speaker. Other quirks require the player to raise the Nunchuk to pump the shotgun. Players need to plant charges (twist the Wii remote like a timer), pick up documents and man various stationary guns. This version also marks the return of the sniper rifle and adds bazookas and mortars.

Up to 32 players can simultaneously join a single match, with game modes such as Death Match, Team Death Match and Infiltration. Multiplayer maps are adaptations of the single-player levels.