Then, he played for Club Atlético Independiente for two seasons before moving to La Liga side, Real Betis.

He was key player of the national team in 1990 FIFA World Cup where Argentina reached the final match of the tournament.

After the tournament, he retired from international career at the age of 30 after collecting 23 caps and scoring 1 goal for the Argentina national team.

He was appointed as head coach of Lausanne Sports, another former club in 2003 but resigned after just five weeks due to poor results.

However, in December 2005, Calderón was fired by the Saudi Arabia Football Federation as they were dissatisfied by the team's poor showing in the 2005 West Asian Games after a defeat to Iraq, and was replaced by Marcos Paqueta.

[2] However, there was no success in the league, as Al-Ittihad were eliminated from the 2008 ACL and lost the final game of King Cup of Champions to Al-Shabab.

He also led the club to the final match of 2009 AFC Champions League, win the Group A and defeated compatriot Al-Shabab 2–1 in the Round of 16.

They faced Pohang Steelers in Tokyo, Japan but was beaten by Korean side 1–2 and finished the tournament as runner-up.

Under his management, Baniyas reached the knockout stage of the AFC Champions League for the first time in the club's history but was defeated by Al-Hilal, Calderón's former side in the Round of 16.

On 28 October 2012, Calderón was announced as head coach of Bahrain national football team to succeed Peter Taylor after the latter's dismissal.

On 19 January 2014, he was appointed as head coach of La Liga side Real Betis, replacing Juan Carlos Garrido.

On 1 July 2019, Calderón was appointed manager of reigning Persian Gulf Pro League and Iranian Hazfi Cup title-holders Persepolis, a post that was left vacant by the departure of Branko Ivanković, who left to manage Al-Ahli Saudi FC.