It ran from 9 to 13 November 2021 in Milan, Italy at the PalaLido and was the fourth edition of the event.

On 14 September 2021, the first four qualifiers were announced: Jannik Sinner, Félix Auger-Aliassime, Sebastian Korda, and Carlos Alcaraz.

[4] After Auger-Aliassime withdrew from the tournament, the ATP announced Juan Manuel Cerúndolo as the next qualifier on 1 November 2021.

[5] Brooksby withdrew due to injury on 2 November 2021 and Sebastián Báez qualified later that day.

Standings are determined by: 1. number of wins; 2. number of matches; 3. in two-players-ties, head-to-head records; 4. in three-players-ties, percentage of sets won, then percentage of games won, then head-to-head records; 5.