Smith will ride the horse, which won the 2011 handicap under the guidance of his former girlfriend, in a bid to regain the title from Ron The Greek.
Game On Dude will partner with jockey Mike Smith to face Ron The Greek
Game On Dude warms up for his run at the Dubai World Cup by trying to wrest back his crown in the Santa Anita Handicap in California on Saturday.
Bob Baffert's six-year-old gelding won the prestigious handicap in 2011 when ridden by Chantal Sutherland.
The son of Awesome Again will attempt to deny Ron The Greek, last year's winner, under the guidance of Mike Smith, Sutherland's ex-boyfriend.
It is the first time in the 76-year history of the event that two previous winners go eyeball to eyeball.
Game On Dude has been burdened with the highest weight in race history and must concede 1.36 kilograms to his main rival.
It is a weight that Smith believes his charge is more than capable of carrying to victory, however, after their impressive success in the San Antonio Stakes at the same venue a month ago.
"He's hit another gear, is really sound and talented," Smith told the Los Angeles Times. "As some horses get older, they get better.
"He seems to have really stepped his game up, with the high speed and the way he finished. He ran within himself and is extremely fit, a healthy, happy horse coming into this race."
The two horses are unlikely to have the race to themselves as among their eight rivals lurks Handsome Mike, the Pennsylvania Derby winner for Doug O'Neill, as well as Called To Serve, who will be ridden by the 1998 Dubai World Cup-winning jockey Gary Stevens in his comeback season.
O'Neill also saddles Richard's Kid, formerly with Satish Seemar.
Follow us @SprtNationalUAE