De Matthaeis spent the majority of his fifteen-year professional career in New York, with short stints in Italy. He was called into the Italian National team training camp towards the end of his career. While he played with the New York Cosmos he enjoyed minutes playing alongside some of the greats like Carlos Alberto, Franz Beckenbauer, and Giorgio Chinaglia. He appeared 38 times over 4 years for the New York Cosmos from 1981 to 1984. During his career with the Cosmos, he scored 17 times and assisted on 12 goals in both indoor and outdoor competitions

 

De Matthaeis coached at IMG Academy in Sarasota, Florida for a number of years, where he developed young athletes in preparation for the next level. In 2014 De Matthaeis moved to Miami, Florida where he became head coach of Miami United FC. During his only year in charge, he posted a record of 7–3–0 and won the NPSL Sunshine Conference. He became the only Miami United FC head coach to go undefeated during the regular season. In 2015 with the help of another ownership group he founded the Miami Fusion FC of the NPSL. He would coach them in their first season of play to an NPSL Sunshine Conference championship over his former team Miami United FC. With this win, he would secure a place for the Miami Fusion FC in the 2016 US Open Cup in their first season. In 2018, Ferdinando joined former teammate Joe Balsamo at the club, becoming the CEO of FA Euro Academy.