After transferring from De Anza College, Simontacchi attended San Jose State University in the 1994–95 school year and pledged the Cal Iota chapter of the Phi Delta Theta fraternity as a member of the Alpha Theta pledge class. Simontacchi completed his collegiate baseball career at the College of Idaho.
He was pitcher of the year in 1998 for the independent Frontier League champions, the Springfield Capitals, going 10-2 with an ERA of 2.95. He also played in the Italian Professional League for Rimini Baseball Club and went 12-1 with a 1.17 ERA in 2000, where he played well enough to make the roster for Italy at the 2000 Sydney Olympics where he was the winning pitcher vs. South Africa, pitched in relief vs. USA and was the losing pitcher vs. The Netherlands with a 1.17 ERA and 10 strikeouts in 15.1 innings.
He had an ERA of 2.34 and a record of 5-1 in 2002 for the Triple-A Memphis Redbirds, a year in which he was mostly up with the 2002 St. Louis Cardinals as a 28-year-old rookie. Through his first 13 starts with the Cardinals, he went 7-1 with a 2.82 ERA. He finished the season with an 11-5 record in 24 starts, and ninth in Rookie of the Year voting. In 2003, he was 9-5, as a part-time starter with 16 starts, with an ERA of 5.56.
Simontacchi suffered right shoulder problems from a torn labrum in 2004, and was released by the Cardinals at the end of the year and he missed the 2005 season.
Simontacchi considered playing for Italy at the 2006 World Baseball Classic, but didn't. He signed a minor-league deal with the Chicago Cubs for the 2006 season, but his contract was voided. However, he pitched 10 games in the independent Atlantic League for the Bridgeport Bluefish with an ERA of 0.84. He then pitched for the Estrellas Orientales in the Dominican Winter Baseball League and in his five starts went 3-1 with a 2.02 ERA over 27 innings.
In 2007, he was a non-roster invitee to the Washington Nationals in spring training, and was projected to be in the Nationals starting rotation, until a groin injury sidelined him. He rehabbed in Triple-A, and when starters Jerome Williams and John Patterson both went on the 15-day disabled list in the space of 10 days, he was called up and started against the Milwaukee Brewers on May 8, a game he pitched well until giving up a 3 run home run in the sixth inning and getting tagged with the loss. In his second start, on May 13, 2007, Mother's Day, he pitched 5-1/3 innings, and collected his first major league win since 2003. By mid-July, he was 6-7 with an ERA of 6.37. He experienced elbow soreness after a start on July 15, and five days later landed on the disabled list due to right elbow tendinitis. Simontacchi became a free agent at the end of the season.
He pitched in the Independent Atlantic League in 2008 with Long Island Ducks
He was a starting pitcher for the Lancaster Barnstormers of the independent Atlantic Baseball League during the 2010 season.
In 2013, Simontacchi became the pitching coach with the Single-A St. Louis Cardinals affiliated Peoria Chiefs. In 2014, he was promoted to Springfield Cardinals AA.