[2] The game starts with the player selecting a boss character, several of which are directly modelled on Prohibition-era criminals such as Al Capone, Dean O'Banion, and Stephanie St. Clair, while others, such as Goldie Garneau, are fictional but take inspiration from the era.

Each boss can form a "crew" of up to 16 underlings from 60 potential ones to help manage their empire of criminal rackets, such as speakeasies, casinos, and brothels, protect them from the law and rival mafia gangs, deal with unforeseen problems (such as protestors shutting down a brothel or an undercover federal agent visiting a speakeasy), and work to extend their gang's influence by taking over the rackets of other bosses.

Deciding how to handle rivals—whether that involves forming alliances with them, paying or threatening them into backing off, or simply killing them and assuming control of their empires—is an important aspect of Empire of Sin.

Each neighborhood has locations where speakeasies and breweries can be established to produce and sell alcohol, and the boss must invest considerable sums to protect them and increase their production capabilities.

[2] Taking over rackets or occupied buildings, as well as getting into shootouts with rival gangs or law enforcement officers, enters the boss and their crew into a turn-based strategy game similar to X-Com.

Members of the crew must be positioned before they can attack or accept any of the player's orders, and can be armed with a variety of weapons, body armor, explosives, and healing items purchased from black market dealers.

Funds earned from rackets can be used to pay off cops, hire lawyers to keep underlings out of trouble, recruit advisors and underbosses who can reduce the player's workload by assuming some responsibilities of managing the empire, and plant moles in other gangs to disrupt their operations.