Zanetti also expressed full confidence in Lionel Scaloni's ability to manage the transition without repeating the mistakes of other World Cup-winning coaches.
The Inter Milan vice-president and Argentina legend was speaking at a pre-final event in Budapest, days before Argentina's tournament campaign is set to begin in the United States.
On Mastantuono, who was cut from Scaloni's 26-man squad in the final round of selections, Zanetti was measured but clear.
"Argentina has great players and when you look at the one who is left out, it's normally a great player. For me, Mastantuono is exactly that, and time is on his side. I think he has many years ahead of him and will surely have the opportunity to play in other World Cups."
Mastantuono, who turned 18 in March, has just completed his first season with Real Madrid. His omission was one of the most discussed decisions of Scaloni's squad announcement.
Zanetti was also asked whether the challenge of defending a title after Qatar 2022 might expose Scaloni to the same pitfalls that affected Vicente del Bosque in 2014, when Spain's 2010 champions arrived without a natural renewal cycle and exited in the group stage. He was dismissive of the parallel.
"I don't think so, because there are players in the Argentina squad who are doing things very well and I think that for a coach like Scaloni, who is very intelligent, he will put out the best players available at that moment."
On Argentina's candidacy more broadly, Zanetti remained in familiar territory.
"It is very complicated to defend a title, but I see an Argentina that will go to the World Cup trying to defend what they achieved in Qatar and to be protagonists."