Kyrgios has been tormented by a succession of injuries in the last two-and-a-half years and only played six singles and three doubles matches since the start of 2023, winning one of each.
But the prospect of the short-form event, and a star-studded cast, has persuaded him to enter along with a series of intriguing pairings.
Only two of the 20 current top-10 male and female players have to date declined to put their names forward in a victory for the organisers' rebrand, the creation of which drew condemnation from regular doubles players including Australia's Ellen Perez.
Men's No.1 Jannik Sinner has paired with American women's world No.9 Emma Navarro and men's No.2 Carlos Alcaraz with former US Open winner Emma Raducanu. Women's No.1 Aryna Sabalenka has linked up with men's No.19 Grigor Dimitrov.
Men's No.9 Holger Rune and women's No.2 Coco Gauff are the current top-10 players not to have entered so far, nor have Australian No.1s Alex de Minaur and Daria Kasatkina - the entry window closes on July 28.
Sixteen teams have signed up with the top eight with the best combined singles ranking guaranteed a place along with eight wildcard entries.
Kyrgios and Osaka would need a wildcard, being ranked 633rd and 57th respectively, but given the revamp is aimed at attracting more fans, viewers and sponsors there is little doubt such a high-profile duo would get one.
"Seeing the teams that have already put their names on the entry list makes us all incredibly excited," US Tennis Association CEO Lew Sherr said. "It shows that the players are behind what we are trying to do, and we know that the fans will love it."
The attraction for many singles players is the shortened format and the timing, the event being played in the "Fan Week" before the main draw.
Most matches will be best-of-three sets played to four games instead of six, with a deciding point played at deuce. Tiebreakers would be at 4-4, while a first-to-10-points match tiebreaker would replace a third set.
The final would be played to six games but still with no-advantage scoring and a 10-point match tiebreaker.
This format, the selection criteria and the clash with singles qualifying, are reasons why established doubles players were unhappy.
"Tell us that you think doubles players are trash, that tradition is overrated and job opportunity is a thing of the past without actually saying it," Perez, a players' council representative, posted on X at the time of announcement.
Defending champions Sara Errani and Andrea Vavassori, who have entered but will need a wildcard given their singles rankings, said the changes were a "profound injustice" that disrespects doubles players, describing the new event as a "pseudo-exhibition focused only on entertainment and show".
"Making decisions just following the logic of profit is profoundly wrong in some situations," they added.
MIXED DOUBLES ENTRY LIST
Emma Raducanu and Carlos Alcaraz
Iga Swiatek and Casper Ruud
Emma Navarro and Jannik Sinner
Aryna Sabalenka and Grigor Dimitrov
Olga Danilovic and Novak Djokovic
Naomi Osaka and Nick Kyrgios
Qinwen Zheng and Jack Draper
Jessica Pegula and Tommy Paul
Jasmine Paolini and Lorenzo Musetti
Elena Rybakina and Taylor Fritz
Mirra Andreeva and Daniil Medvedev
Madison Keys and Frances Tiafoe
Paula Badosa and Stefanos Tsitsipas
Belinda Bencic and Alexander Zverev
Taylor Townsend and Ben Shelton
Sara Errani and Andrea Vavassori
