[2] Santa Cruz was a member of the club's first-team for the 2008 season, also with several other youth team graduates as Rodrigo Burgos, Celso Ortiz, Ivan Piris and Luis Caceres.
[4] Manager Paul Ince had completed the deal for Santa Cruz for the 2008–09 season where which he would play alongside his brother and the transfer was subject to international clearance.
[12] Four days later, Santa Cruz featured as a second-half substitute in Nacional's second Copa Libertadores group stage fixture, a 1–0 home victory against Venezuela club Zamora on 20 February 2014.
Santa Cruz later stated that the goal was the most important one of his career and that after the match he received a message of congratulations from older brother Roque.
[20][21] During the second–leg on 13 August, Santa Cruz was substituted onto the field in the 85th minute of the match for Julián Benítez as Nacional were ultimately defeated 1–0.
Two weeks later, Santa Cruz scored his fourth league goal of the 2014 season against former side Deportivo Capiatá on 5 October.
Santa Cruz, who was in the starting eleven of the fixture, scored in the 43rd minute to give Nacional a 1–0 lead as they went on to claim a 3–2 away victory.