He made his Ligue 2 debut on 18 October 2013 against CA Bastia replacing Bryan Bergougnoux after 88 minutes in a 2–1 away win at the Stade Armand Cesari.

[4] In September 2020, Santamaria moved to Bundesliga club SC Freiburg after protracted negotiations with Angers.

[5][6] German sports magazine kicker reported the transfer fee as "about €10 million", the highest in SC Freiburg's history.

[6] On 17 August 2021, Santamaria transferred to Ligue 1 club Rennes for a reported fee of €14 million.

[7] On 22 January 2025, Santamaria was loaned to Nice for the remainder of the 2024–25 season, with an option to buy.