It's a clash that has led some drivers facing a stick-or-twist dilemma: tackle the narrow, hair-raising corners on the Riviera, or test their stamina over the famous 500-mile, 200-lap endurance contest on the other side of the Atlantic.
Only five drivers have won both a Formula One world championship and the Indy 500. Two-time F1 champ Fernando Alonso will be hoping to make that six and become just the tenth rookie to lift the iconic Borg-Warner trophy on the race's 101st anniversary.
That Alexander Rossi -- an Indy 500 rookie and F1 convert -- triumphed last year will give the Spaniard hope, while McLaren Executive Director Zak Brown has also said he thinks his driver can win
at the Brickyard on May 28.
Indeed, the Indy 500 might prove to be a breath of fresh air for Alonso after a disappointing few seasons in F1. He finished 10th in the drivers' championship last year, and is yet to register a point over five races in 2017 as McLaren has struggled to match the advances made by its rivals.
If he were to triumph, a place in the history books would beckon. Since Jim Clark won the 1965 race, Graham Hill, Mario Andretti, Emerson Fittipaldi and Jacques Villeneuve have also gone on to win both F1 championships and the Indy 500.
Among them, Hill is the only man to win motorsport's famed Triple Crown, recording victories at Monaco GP, the Indy 500, and Le Mans 24 hours.
Alonso has set his sights on joining the Brit. Can he swap champagne for milk, F1's shortest race for one of motorsport's longest?
The stage is yours, Fernando.