On 1 September 2008, just a few minutes before the transfer window closure time, Genoa completed the transfer of Milito from Zaragoza after the Spanish team were relegated to the Segunda División. His agent, Fernando Hidalgo, confirmed Milito chose explicitly to return to Genoa despite having received more lucrative offers from other major European clubs. He made his Serie A debut on 14 September against Milan. Genoa won the game 2–0 with Milito assisting the first goal and scoring the second. On 9 November, Milito scored his first hat-trick for Genoa in the 4–0 victory against Reggina. He finished the season with 24 goals in 31 league appearances, placing him second behind Zlatan Ibrahimović in the "Capocannonieri" scoring title.