The iconic trio of Cooper Cronk, Cameron Smith and Billy Slater have all retired from representative rugby, while Michael Morgan has suffered a season-ending pectoral tear.
As such, Meninga is keeping a close eye on the Origin series, which New South Wales Blues lead 1-0 after game one.
"A lot of weight will be placed on the Origin series this year and who wins it," Meninga said.
"Particularly around the spine, your nine, seven, six and one. Some of our greatest ever players have retired so our spots are wide open."
The return of Greg Inglis following a long-term knee injury is a boost to Meninga and the Kangaroos, particularly with a new captain needed following Smith's retirement.
"[Inglis] was excellent [in game one] and that's what you expect from him, to lead from the front," Meninga added.
"Behind the scenes, he's very intelligent and can send a message out to his troops."
Photo Getty Images. Caption: Mal Meninga