The House is the main antagonistic force to the Teambase, a Shadaloo-esque criminal syndicate with heavy stake in the casino real estate business, among many other dastardly fields. Led by the Donna, Lady Lucy, its main governing body is mostly bodyguards since Lucy trusts her bodyguards more than anything. These bodyguards include the Bridesmaids Cassandra and Cordelia, the disgraced samurai Honjo Masamune (Sam's father), and The Letterman, a cryptic masked biker who is seemingly much higher in rank than she should be for unknown reasons.

The snake-like Synth Mr. Reeds handles most of the day-to-day criminal management, while the eccentric "Pam" handles their growing biotech industries.

At the lowest ranks of gang executive management are the Casino Bosses, who run the various Casino bases for the House across the galaxy and serve various other roles. Misir, a scarab ex-model, handles general security. Vergil, a human crimelord, is the main battle strategist, and Fernando Fontaine, fishman wise guy, handles the gang's finances.