The Wiseguys are a new gang in Stilwater , whose members are primarily Italian, Sicilian, and Italian-American. Their gang color is black, and most members wear black track suits, silver chains, sunglasses, and either flat caps or fedoras. Their favored radio stations are Klassic 102.4 and the new Oldies 92.1, which plays music from the 1950's and 1960's. They are wealthy, powerful, and generally well-armed. They drive black sedans, and their leader, Nino Genova, drives a black limousine.

The Wiseguys are traditionally based in Italy, near the city of Rome, although most Mafia families are based in Sicily and Naples. They mainly deal in gambling, gunrunning, pimping, extortion, stolen goods, and white collar crimes. The Wiseguys avoid the drug trade at all costs though. Traditionally, they are allied with the Third Street Saints and negotiated an alliance with the Deckers, and their main enemies are the Luchadores, Morningstar, Vice Kings, and The Syndicate. Wiseguys tend to be less thuggish than most gangs, but are just as fierce and better organized.

Their leader is the charismatic and intelligent Nino Genova, an Italian immigrant and founder of the Wiseguys.