First nominations for the $5 million All-Star Mile will be taken this week ahead of the third running of the unique race.

The All-Star Mile will be held at The Valley for the first time with nominations for the $5 million race opening this week.

Connections can enter qualified horses from Wednesday until January 11 before the general public votes on who they want to run.

The 10 most popular horses will gain spots in the field alongside five wildcard runners who can win their way into the race via qualifying events, or through being chosen by an All-Star Mile wildcard panel.

Flemington hosted the inaugural running in 2019, which was taken out by Mystic Journey, and as part of the event's track rotation system, it moved to Caulfield this year where it was captured by West Australian raider Regal Power.

Greg Carpenter, RV's executive general manager racing, anticipates both winners to be in the mix again if they are nominated

"We expect both Mystic Journey and Regal Power will prove popular with voters if they are nominated again this time, whilst we expect to see some of the stars of the spring, along with some left field entries, put their claims for The All-Star Mile 2021 in the hands of the voting public," Carpenter said.

Connections pay a $500 nomination fee, donated to the Good Friday Appeal which supports Melbourne's Royal Children's Hospital.

Horses entered for the race need to meet several criteria, including having placed in a stakes race.

The winners of the Group One Futurity Stakes (1400m) at Caulfield and Group Two Blamey Stakes (1600m) at Flemington will both earn automatic starts.

The public will be allowed to cast their votes from January 22 until February 14 with more than 275,000 voting over the first two years.