He most prominently played for Milan, with whom he won four Serie A championships and two UEFA Champions League titles, as well as in France's Ligue 1 for Paris Saint-Germain and Monaco.

In the summer of 1989, Simone was brought into the squad of third-place finishers AC Milan by manager Arrigo Sacchi.

Despite competing for the attacking spots at Milan with the three FIFA World Player of the Year award winners Marco van Basten (1992), Roberto Baggio (1993) and George Weah (1995) (as well as the presence of Ruud Gullit, Dejan Savićević, Daniele Massaro, Paolo Di Canio, Jean-Pierre Papin, Christophe Dugarry, and Brian Laudrup), he scored a total of 74 goals in 245 games in all competitions for Milan.

[1][3] In 1997, Simone moved abroad to play for French club Paris Saint-Germain, with whom he won both domestic cups in his first season.

He scored 21 goals and made 15 assists in 34 games during the 1999–2000 season, and helped Monaco win the Ligue 1 championship in 2000.

He returned to Milan for parts of the 2001–02 Serie A season, scoring his last goal with the Rossoneri in Coppa Italia against Lazio in 2002.

[1][6] Simone was a diminutive forward, gifted with pace, good movement, an eye for goal, and excellent technique.

[9] He was fired at the end of the season with the club having finished 8th and not met their aim of instant promotion, despite the investment of billionaire new owner Dmitry Rybolovlev.

[10] Simone became Technical Director at Lausanne-Sport of the Swiss Challenge League in November 2013, and 11 months later he replaced Francesco Gabriele as manager.

[25] Châteauroux was in last place at the time he was hired, and remained in that position until the end of the season, getting relegated to the third-tier Championnat National.