The two Mexico stars were the headliners of 28-man roster selected to represent MLS, but injuries will keep them out of the match set at Banc of California Stadium in Los Angeles.
Hernandez has not played since June due to a calf injury, while Vela suffered a setback to a lingering quad injury in a match on Saturday at Vancouver.
This year's team was determined by fan, player and media voting; MLS All-Star head coach Bob Bradley of hosts LAFC; and MLS commissioner Don Garber.
"Carlos' quad has bothered him throughout this season," Bradley said. "We were very cautious. It's just a lingering injury that has hampered him throughout the season."
New England Revolution duo Carles Gil and Tajon Buchanan have also pulled out of the fesitivites in L.A. The league announced that Inter Miami CF midfielder Rodolfo Pizarro and Atlanta United FC defender George Bello have been added to the roster.
Liga MX confirmed its roster last month, made up of nominees for the league's players of the season, as well as selections from Liga MX All-Star manager Juan Reynoso of Cruz Azul. Among those chosen are Tigres star Andre-Pierre Gignac and Club America keeper Guillermo Ochoa.