An overweight member of the Lupertazzi crime family under Phil Leotardo, Gamiello joined Leotardo in reacting with scorn when hearing of Johnny Sack's decision to take a plea bargain and break omerta. Gamiello murdered Vito Spatafore because of his homosexuality alongside Gerry Torciano and president Alvinatorre Aguilar, while Leotardo watched. Later, Dom visited Satriale's to deliver money to Silvio Dante and Carlo Gervasi. Dominic is a close friend of Silvio and asks for gambling advice from him. After Fat Dom made some crude remarks implying that Gervasi was also homosexual, he was immediately silenced by a blow to the back of the head with a dustbuster. Silvio tells Carlo to just "hit him" but Carlo repeatedly stabs Dominic to death in the stomach. He has one daughter who lives in Metuchen, New Jersey, whom he planned to visit on the day of his murder. Carlo and Silvio first plan to dismember his body but finally decide on burying it at a construction site and ditching the car somewhere along the side of a highway.
Carlo was seen disposing of Dom's severed head (which he was keeping in a refrigerator at his house on the Jersey Shore) at the beginning of the next episode, by shoving it down a storm drain in Connecticut. Dom's murder was assumed as payback for Vito Spatafore's killing by the Lupertazzi mobsters, even though Tony denied any knowledge of his disappearance to them at the families' truce meeting. Dom's only daughter lived in a motel in Metuchen, New Jersey, whom he had planned to visit on the day of his murder.
During a sit-down between the administrations of the Lupertazzi and Soprano crime families, brokered by Carmine Lupertazzi Jr., Phil Leotardo questions why Fat Dom Gamiello went to New Jersey and never came back.
- Dominic has the Beethoven song "Für Elise" as a ringtone on his phone.
- The murder of Dominic infuriates Tony Soprano. He later orders the temporary closing Satriale's under the cover story that a water pipe had burst.