The Repsol Honda rider has impressed many since stepping up from the Moto2 class and holds a 16-point lead at the top of the championship points standings over team-mate and fellow Spaniard Dani Pedrosa.
The focus will also be on another Spaniard, defending champion Jorge Lorenzo, who races for only the the second time following a second operation on his injured collarbone.
The Yamaha factory rider finished sixth in the last round at Laguna Seca in California where Marquez took the race win ahead of the three-week summer break.
Lorenzo suffered the injury ahead of the Dutch TT at Assen but underwent surgery before taking part in the race, only to bend the plate when he crashed during practice for the next round at the Sachsenring in Germany.
Lorenzo was forced to sit out the Sachsenring race following more surgery and Pedrosa also missed out after suffering concussion and a shoulder injury.
The latter ailment hampered Pedrosa at Laguna Seca where he finished fifth, one place ahead of Lorenzo who now trails him by 10 points in the standings.
Rather than worry about the problems of his two title rivals, however, Marquez is focusing on himself.
"After a good break, where I've managed to relax a little and also do some training, I'm looking forward to getting back on track," said Marquez.
"It's been good to have this time off to think about my first few months in MotoGP and reflect on my performances and what I've learnt but now I'm ready to get back on the bike.
"I like the Indianapolis track and I'm interested to see how the grip is on the Bridgestone tyres because it seems this has been an issue in the past."
Marquez's team-mate Pedrosa has taken the summer break to aid his recovery from injury.
He said: "It's been a good summer break and I'm feeling much stronger physically. I've had time to relax with some friends and also have lots of physiotherapy on my shoulder to prepare myself for this second part of the season.
"I've had a medical check in the last days and we can see the bone getting stronger. It still needs a few more weeks to recover completely but my feeling is already much better than in Laguna."
Indianapolis will also be the first race since Ducati announced the signing of British rider Cal Crutchlow who moves from the Monster Tech 3 Yamaha team at the end of the season on a two-year deal.