The Italian will not even have to face Carlos Alcaraz, who beat him in a dramatic Roland Garros final last year, after his great rival was ruled out through injury.
Sinner could become the ninth man to complete the set of all four major titles, following in the footsteps of Alcaraz, who achieved the feat at the Australian Open earlier this season.
The world number one could not be in better form after romping to the Italian Open crown on Sunday.
That final victory over Casper Ruud made the 24-year-old only the second player to win all nine Masters 1000 tournaments after Novak Djokovic, who is arguably his biggest rival for the French Open, which starts on Sunday.
Sinner has won six consecutive Masters titles and is on a record-breaking 34-match winning streak at the level just below the Slams.
It would be a surprise if he cannot translate that form to the red dirt in Paris.
Sinner cruised into the 2025 final without dropping a set before missing three championship points as Alcaraz staged a remarkable comeback from two sets down to snatch the trophy.
Norway's Ruud, who has never taken a set off Sinner in five meetings, is under no illusions as to the task facing the other contenders for the Coupe des Mousquetaires.
"I never played the big three in their prime... But I'm sure Roger (Federer), Novak, Rafa, 25, 26 years old, were also the same feeling for the other players," said Ruud of Sinner after being swatted aside 6-4, 6-4 in Rome.
"I don't see him getting any worse, unfortunately. You just have to think that you have to be better and better because he's also going to get better and better."
Sinner has only lost twice in 10 tournaments since retiring injured against Tallon Griekspoor in Shanghai last September.
Czech Jakub Mensik got the better of him in the quarter-finals of the ATP event in Doha in February, while Djokovic produced a vintage display in the Australian Open semi-finals.
Djokovic still targeting record
Djokovic is still the most likely man to deny Sinner, despite having struggled for form and fitness since losing to Alcaraz in the Melbourne final.
The Serb, who will turn 39 shortly before the tournament, has beaten Sinner five times in 11 meetings.
Djokovic, still chasing a record-breaking 25th Grand Slam title, has made at least the semi-finals at each of the past five majors.
But he remains without one of the sport's biggest four trophies since equalling Margaret Court's all-time record tally at the 2023 US Open.
Djokovic, now ranked fourth, has only played two events since the Australian Open, losing to Jack Draper in the Indian Wells last 16 before a surprise defeat by Croatia's Dino Prizmic in his opening match in Rome.
Alexander Zverev will be the second seed in Alcaraz's absence and will have high hopes of finally ending his wait for a maiden Grand Slam title.
But there is little to suggest the German can start delivering when it matters.
The world number three has lost in three finals and nine semi-finals since last winning an ATP tournament in Munich 13 months ago.
Zverev has lost nine successive meetings with Sinner and the last six in straight sets.
Home hopes will be high for a deep run from Arthur Fils, who has enjoyed an excellent return from injury this season.
There has not been a French men's quarter-finalist since Richard Gasquet in 2016.
Spanish teenager Rafael Jodar will be seeded at a Grand Slam for the first time after an impressive clay-court campaign, while Brazilian fans will turn out in numbers to support their rising star, Joao Fonseca.
However, everything points to Sinner standing with the trophy on Court Philippe Chatrier on June 7th, which would leave an Olympic gold medal as the only big achievement missing from his still young career.