Zampese joined the St. Louis Rams in 2000 as an offensive assistant under head coach Mike Martz. He was promoted the following season to WRs coach, and again the next season to WRs coach/passing game coordinator. During his stint in St. Louis, Zampese assisted Martz with the passing game of what became known as "The Greatest Show on Turf" – a nickname for the Rams' high-powered, record-setting offense. It was here that he gained additional exposure to the "3-Digit" passing system, pioneered by his father and expanded to new heights under Martz.
Although "The Greatest Show on Turf" began its record-setting run a year prior to Zampese's arrival in St. Louis – the 1999 Super Bowl XXXIV Rams' Super Bowl championship season – it lasted three seasons (1999–2001), and he was with the Rams for the final two seasons of the run (2000–01).
Cincinnati Bengals
Zampese joined the Cincinnati Bengals in 2003 as quarterbacks coach at a time when the team was searching for a quarterback to lead the franchise. He aided in the scouting and evaluation of the quarterbacks in the 2003 NFL Draft, as the team used its No. 1 overall pick to select 2002 Heisman Trophy-winning quarterback Carson Palmer of Southern California. On September 15, 2017, Zampese was fired by the Bengals after the team started the season 0–2 and did not score a single touchdown.[3]
Cleveland Browns
On January 12, 2018, Zampese was hired by the Cleveland Browns as quarterbacks coach, reuniting him with Browns head coach and former Bengals offensive coordinator Hue Jackson.[4] After the 2018 season, during which Jackson was fired, he was not retained by new head coach Freddie Kitchens.[5]
In 2020, Zampese joined the Washington Football Team as their quarterbacks coach.[8] In 2023, Zampese was given a senior offensive advisor/game management role.[9] He was not retained following the firing of Ron Rivera and hiring of new head coach Dan Quinn.
Atlanta Falcons
Zampese was hired as a senior offensive assistant for the Atlanta Falcons in 2024.[10]