Attending Catawba College, Tomsula played defensive end from 1987 to 1990, after transferring from Middle Tennessee State University after the 1986 season.

In 2007, the San Francisco 49ers hired Tomsula to serve as their defensive line coach and he remained in that role through the 2014 season.

On January 14, 2015, Tomsula became the 49ers' head coach,[8] succeeding Jim Harbaugh, who had been fired by 49ers CEO Jed York.

Tomsula faced heavy restrictions due to the COVID-19 pandemic in terms of physical contact with the players, their availability due to a positive test for COVID-19 or having been exposed to someone who had it, a reduced training camp schedule and the cancellation of preseason games, which made it difficult to implement the new defensive scheme.

[18] In the 2022 preseason, the management of the new Rhein Fire announced that Tomsula would be the first head coach for the upcoming season of the European League of Football.

[19] In their inaugural season, Tomsula coached the expansion Rhein Fire to a 7–5 record, the second best in the Southern Conference though the team failed to qualify for the playoffs.

[21][22] He is a devout Roman Catholic, but does not push his views on others, stating: "God takes care of everything...I don't give anyone religion lessons.