In the future, Mankind has developed special androids called A.D.A.Ms (Autonomous Dueling Armed Machine) to fight their wars for them, thus putting an end to centuries of bloodshed. Unfortunately the A.D.A.Ms were a little too effective, and have since completely eliminated the need for war altogether. Not content to just scrap the remaining androids (for some unknown reason), a tower was constructed and used to house the surviving killing machines. Trapped in this tower, the A.D.A.M androids are made to fight each other to the "death" much like Roman Gladiators, only without a prize if they win.

The core gameplay of Rengoku 2 is pure action. Your A.D.A.M begins with nothing but his fists to fight off the other androids in the tower. As you defeat your enemies, they sometimes drop Elixer Skins (which can be used to upgrade your health, defense and more) or weapons. Once you've gathered a few weapons you can go back to a terminal (the hub at the beginning of every floor of the tower) and equip them. Weapons can be equipped on the arms, the head or the torso, and certain weapons can be used in multiple places (i.e. the Auto Crossbow can be equipped on your head and/or your arms but not your torso). Each section of the body is assigned a face-button (Square - Left Arm, Circle - Right Arm, X - Torso and Triangle - Head). This can lead to some nasty combos if you link your weapon attacks together. By racking up big combos as your opponent dies (this is called "Overkill"), you can increase the chance that they'll drop more Elixer Skins or that Flamethrower you saw them using a few seconds before you back-flipped to a safe distance and hit them with a barrage of homing missiles.

The game's pacing is also as straight-forward as its gameplay. You clear the current floor of enemies (gathering weapons and upgrading along the way), fight the floor boss, then move up to the next floor to do it again. As you progress through the tower, your enemies begin using more powerful weapons, which you can take for yourself of course, and even start to attack you in groups.

There is also a multiplayer mode which uses the game-sharing feature so you can actually upload a demo to your friend's PSP if they don't own the game themselves. Multiplayer is a straight deathmatch affair. Each player begins with nothing, finding weapons and support items in the environment or inside destructible crates. The pickups all look the same, so there's no way of knowing what you're about to pick up until you actually take it, which adds a bit of random, on the fly strategy to the multiplayer.