He debuted in the Italian Serie A championship for Como on 11 January 1987. After a few appearances in the top-flight Serie A, he was put on loan at Virescit Boccaleone in the secondary Serie C1 league. He scored 15 goals for Virescit in the 1987–88 season, and finished as top scorer of the Serie C1 league.
During his time with Milan, Simone also made his senior debut for the Italian national team on 19 December 1992, under then national team manager Arrigo Sacchi, in a 2–1 away win against Malta. He would go on to play four games for the national team between 1992 and 1996, but did not score any national team goals.
In 1997, he moved abroad to play for French club Paris Saint-Germain, with whom he won the 1998Coupe de France. He transferred to AS Monaco in 1999. He scored 21 goals and made 15 assists in 34 games in the 1999–2000 season, and helped Monaco win the French Ligue 1 championship in 2000. He returned to AC Milan for parts of the 2001–02 Serie A season, though he did not score any goals in his short spell. He returned to Monaco, but rarely played during the 2002–03 Ligue 1 season.
Following an unsuccessful season playing for OGC Nice, he retired from football in 2004, at the age of 35. He made a short come-back as he played a single game for Serie C2 club Legnano in 2005.
In 2005 he acquired Legnano, becoming shareholder at the club and also appearing once as a player. As a board member, he contributed to guide Legnano back to Serie C1 in 2007.
He successively became a FIFA-licensed football agent and, in 2009, a market consultant for his former club AS Monaco FC. In September 2011, Monaco offered him the head coaching role in attempt to turn the fortunes of the club, freshly relegated to Ligue 2 and last-placed in the second French tier. He was confirmed also after the club takeover led by Russian billionaire Dmitry Rybolovlev, but sacked at the end of the season.