On 14 February 2018, at the age of 14, Mantzoukas began his pro career with Promitheas Patras, in the Greek Basket League, during the 2017–18 season.

Three months later, on 24 May 2017, while still at the age of 13, Mantzoukas became the youngest player to ever start a game in the top-tier level Greek League, since it became fully professional in 1992.

[5] On 10 October 2018, at the age of 15, Mantzoukas debuted in one of the two European-wide secondary level competitions, the FIBA Champions League, during the 2018–19 season.

He made his EuroCup debut in a game versus the Israeli Super League club Maccabi Rishon LeZion, in which he scored 2 points.

During the 2022–2023 campaign, in 29 domestic league matches, Mantzoukas averaged 5.5 points and 2.4 rebounds (shooting with 41% from the 3-point line) in 18 minutes per contest.