Take on the role of 50 Cent as he gets caught in a web of corruption, double-crosses and shady deals that lead him on a bloody path through New York's drug underworld. Working with the unlikeliest of allies, the streets heat up as 50 takes on the most dangerous crime families in the city, uncovering an international conspiracy with devastating implications. Intended exclusively for mature players, this unapologetically violent game features the monetarily monikered rapper in its starring role, as a streetwise tough seeking revenge against a mysterious gang of thugs that filled him with lead and left him for dead. The hero can gain access to a variety of firearms and other weapons, and can learn more than 25 deadly reversal moves. In the third-person shooter style of the popular 128-bit generation Grand Theft Auto games, players follow a series of missions that lead them through the game's storyline. Bulletproof features previously unreleased music and video by 50 Cent, and the game allows players to set up their own music and video play lists of this included material. The voices and likenesses of other famous musicians portray supporting characters, including Lloyd Banks (lock pick), Tony Yayo (demolitions expert), and Young Buck (weapon specialist) as members of 50's G-Unit posse, Eminem as the "shady" Detective McVicar, and rap music luminary Dr. Dre as the wizened back-alley arms dealer Grizz.

You are the rapper 50 Cent in the streets of New York. You receive a urgent page for one of your old cell mates K-Dog, which leads you into a ambush where 50 Cent gets shot nine times and is left to die. After 50 survives you are back out in the streets sneaking for revenge. 50 gets caught up in a underground world working along side with G-Unit soldiers Lloyd Banks, Young Buck, and Tony Yayo. You go through the game dealing with shady deals and people while taking on the most dangerous crime organization in all of New York City. 50 puts in work to uncover the truth behind the international conspiracy that is being fueled by the streets.