Australia's crushing 2-0 Test series defeat against Pakistan - including a massive 356-run second Test loss - means their shorter-format fixtures against South Africa have become crucial to building up confidence ahead of next year's ICC World Cup.
Coach Darren Lehmann will be without his entire Test squad for the games - three T20s and five one-day internationals - meaning the likes of David Warner, Mitchell Johnson and Glenn Maxwell are unavailable.
But Australia selector Rod Marsh feels they have chosen a squad from the players who have proved themselves in the domestic limited-overs cricket.
"The squad itself includes a good blend of youth and experience, providing [T20 captain] Aaron [Finch] with multiple options with both bat and ball," Marsh said.
"We've seen some good form in Matador One-Day Cup recently from players such as Cameron White, Nathan Reardon, Ben Dunk and Ben Cutting and they've been rewarded for those good performances."
South Africa, meanwhile, will be looking to bounce back from their 22-run defeat at the hands of a young Cricket Australia XI side in their warm up match in Sydney on Sunday.
That loss will not help the Proteas build the "momentum" coach Russell Domingo is looking for ahead of a tough Australia tour.
"If we can get some good results under our belts in the T20 campaign, we can take a lot of confidence into the one-day series," Domingo said.
But South Africa's T20 captain JP Duminy has backed his new look squad to come good against Australia and prove themselves ahead of the World Cup.
"The guys that have been picked for the series have been putting in some outstanding work in the domestic scene back home," he said.
"They deserve their call up; even though there are some guys who are being rested for the series.
"It"s a great opportunity for them to stake a claim within the Proteas set-up, any game you represent your country in is an important one.
"There's quite a few new faces around so it's definitely a great opportunity for guys to put up their hands for the World Cup."