Having secured the ODI series, Pakistan will be looking to keep the winning momentum going when they lock horns with South Africa in the first game at The Wanderers Stadium on Saturday.
The visitors will start the shortest-format series as favourites after clinching the 50-over series 2-1.
The series will help both sides fine tune their preparations for ICC World T20, to be held in India in October this year.
South Africa suffered a blow ahead of the opening T20I when their skipper Temba Bavuma was ruled out of the series after picking a hamstring injury.
In his absence, wicketkeeper-batsman Heinrich Klaasen will lead the hosts who are already without the services of the likes of Quinton de Kock, Kagiso Rabada, David Miller and Anrich Nortje.
Meanwhile Pakistan, Pakistan are expected to bring in Fakhar Zaman, who was not originally included in the T20 squad, after the swashbuckling left-hander notched up back-to-back hundreds in the last two ODIs.
His inclusion in the playing XI means Sharjeel Khan, who last played for Pakistan in 2017, will have to wait further to represent the national side.
The return of veteran batsman Mohammad Hafeez will give the much-needed boost to the middle-order.
Shaheen Shah Afridi, Hasan Ali and Mohammad Husnain are expected to form a three-pronged pace attack while Usman Qadir is likely to solely handle the spin responsibilities.
Pakistan registered a 2-1 victory in the T20I series when South Africa visited Pakistan for limited-overs series in February-March this year. The head-to-head record between the two sides reads 9-6 in favour of South Africa.
The second of four T20Is is scheduled at the same venue on Monday.
Babar Azam (Captain), Fakhar Zaman, Mohammad Hafeez, Haris Rauf, Hasan Ali, Asif Ali, Faheem Ashraf, Shaheen Afridi, Usman Qadir, Mohammad Rizwan (Wicketkeeper), Haider Ali
Heinrich Klaasen (Captain & Wicketkeeper), Aiden Markram, Pite van Biljon, Kyle Verreynne, Andile Phehlukwayo, Lizaad Williams, Wiaan Mulder, George Linde, Janneman Malan, Beuran Hendricks, Tabraiz Shamsi, Daryn Dupavillon.