Take a tank skydiving, call in a satellite-targeted airstrike on a Mexican wrestling gang, and defend yourself against a highly trained military force using only a sex toy in the most outlandish gameplay scenarios ever seen, igniting a city-wide war that will set Steelport on fire. Refusing to kneel to the Syndicate, you take the fight to Steelport, a once-proud metropolis reduced to a struggling city of sin under Syndicate control.

The Syndicate, a legendary criminal fraternity with pawns in play all over the globe, has turned its eye on the Saints and demands tribute.

The Saints are kings of Stilwater, but their celebrity status has not gone unnoticed. Years after taking Stilwater for their own, the Third Street Saints have evolved from street gang to household brand name, with Saints sneakers, Saints energy drinks and Johnny Gat bobblehead dolls all available at a store near you. Professor Genki, a character from the Professor Genki's Super Ethical Reality Climax Activity, has served as an unofficial mascot for the game, and has two vehicles and a weapon named after him.

Whereas the previous games charted the 3rd Street Saints' rise to power over Stilwater, Saints Row: The Third charts their adventure in a new city: Steelport. Like the previous two games in the series, Saints Row and Saints Row 2, the game is an open-world sandbox. The game begins with the player 'on top of the world, right at the beginning of the game, with all the perks that go along with being the head of an elite criminal organization'.

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