Milito began his club career in Argentina with Racing Club in 1999, and later moved to Italian side Genoa in 2003. In 2005, he was acquired by Spanish club Real Zaragoza, where he remained for three seasons, before returning to Genoa in 2008. His prolific goalscoring exploits during his second spell with Genoa earned him a move to defending Serie A champions Inter Milan, where he was pivotal in the club's 2010 treble-winning season, scoring 30 goals in all competitions, including two goals in the 2010 UEFA Champions League Final. He returned to Racing Club in 2014, where he retired in 2016. At international level, Milito earned 25 caps for Argentina, scoring 4 goals, and represented his country in two Copa América tournaments, winning a runners-up medal in 2007, and at the 2010 FIFA World Cup.