The genius scientist Mother Gun has invented a formula that greatly enhances strength, reaction, and durability of the human body. Thus, it became possible to create super-human soldiers. Mother Gun has founded the Freakishly Rugged Advanced Genetics Galactic Enforcement Division (F.R.A.G.G.E.D), whose goal is to protect the galaxy from the onslaught of a terrorist organization known as the Tyrannical Oppressors of Life (T.O.O.L). The terrorists are after Xplodium, a rare element that allows creation of extremely powerful firearms. Two special agents, codenamed Percy and Francis, are sent to stop the evil once and for all.

Gun Bros is a shooter in which the player controls a 3D character moving around top-down environments. The player can choose to control either Percy or Francis; the other soldier is always controlled by the AI. Even though the soldiers can move, exploration is not the focus of the gameplay; rather, the soldiers move around the area, shooting at the enemies until they are all eliminated. Money is gained by killing enemies; they can be spent between missions to purchase better guns, armor, and power-ups. There is also a rudimentary experience system: the soldiers gain Xplodium (XP) with each kill, eventually leveling up and increasing their health bars.

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