Romano is one of the most successful restaurateurs in U.S. history, having founded multiple restaurant chains with a national or international reach. His biggest successes to date are Fuddruckers, Romano's Macaroni Grill, and EatZi's. Romano has founded more than twenty different restaurant concepts in his career.
Romano was also one of the earliest investors in the heart stent. His initial $250,000 investment returned millions of dollars in royalties.