After a long series of promotions, with Pisa, Brescia and Cremonese among them, and good results with outsider teams (Cremonese again, and Napoli), Simoni was called by Massimo Moratti to coach Internazionale of Milan in 1997. With a good-shape Ronaldo on his side, Simoni won a UEFA Cup and gained a controversial second place in the Serie A division when Internazionale lost against Juventus.
Simoni was fired by Internazionale on November 30, 1998, even though being still appreciated and well-remember by the team fans.
After a few other experiences, included a brief disappointing one in Bulgaria with CSKA Sofia, Gigi Simoni has led Ancona Calcio to Serie A in 2003, but has surprisingly been fired before the start of the new season. His Serie A comeback, in 2004, with Siena, was not particularly good, as he was again fired during the season. In late 2005, Simoni took the head coaching role of Serie C1 team Lucchese with little success.
On February 2009, at the age of 70, Simoni accepted a job at Lega Pro Seconda Divisione's Gubbio, where he will serve as technical director until the end of the season. He was later confirmed to his role also for the 2009–10 season, with former Genoa defender Vincenzo Torrente acting as "on-pitch" head coach. Under the guidance of Simoni and Torrente, Gubbio ensured a historic promotion to Serie B that year; after Torrente decided to accept an offer from Bari, Simoni and Gubbio agreed to appoint Fabio Pecchia as new head coach.
Pecchia's term as Gubbio boss turned out however unsuccessful, and on 18 October 2011 Simoni agreed to serve as caretaker head coach for a Serie B game against his former club, league toppers Torino. The game ended in a surprising 1–0 win for his side, and led the club to keep Simoni in charge as long as a valid replacement coach would be found. The following two games led Gubbio to win four more points, a draw and a win. He guided the team until 20 March 2012, when he handed over his first team duties to assistant coach Marco Alessandrini, and moving back to his previous role of technical director at Gubbio.