Rafael Nadal opens his Rome challenge on Wednesday against 27th-ranked Pablo Carreno Busta, after a six-month break from tennis.
Nadal has won the Foro Italico a record nine times, including the last two editions, but could be a little rusty against Busta, who received a first round bye for his exploits in New York.
And with US Open finalists Dominic Thiem and Alexander Zverev both withdrawing from the event, which is being played behind closed doors, there are two main contenders: Nadal and Novak Djokovic.
The Serb is still smarting after his disqualification from the US Open, so will be focussed on winning here.
His first opponent will be against either Italian Salvatore Caruso or a qualifier, with a potential semi-final clash against Gael Monfils or Stan Wawrinka.
Nadal, with a 61-6 tournament record, could play either third seed Stefanos Tsitsipas or seventh seeded Italian Fabio Fognini for a place in the final.
Former French Open champion Simona Halep tops the women’s event.
But she will face opposition from defending champion Karolina Pliskova and two-time Rome winner Elina Svitolina.
Serena Williams withdrew due to the Achilles injury she sustained in New York.
Others to miss the Rome event include 2019 US Open winner Bianca Andreescu, Petra Kvitova, world No.1 Ash Barty and new US Open champion Naomi Osaka.
Halep will face either Anastasija Sevastova or Jasmine Paolini in the second round.
Highlights of early rounds include an interesting clash between Garbine Muguruza opens against American Sloane Stephens.
The 1999 champion Venus Williams has a tough start against US Open finalist Victoria Azarenka, with the winner taking on third seeded Sofia Kenin.