Matsatsantsa booked their place in the semi-finals after beating Kaizer Chiefs 1-0 on Saturday night.
The clash between City and Wits will see Benni McCarthy come up against his former coach in Gavin Hunt.
Hunt unearthed Benni as a player over two decades ago. The former Bafana Bafana forward went on to become one of South Africa's best exports in the early 2000's.
The Students beat City in the semi-finals of last year's edition, and the Braamfontein-based outfit should be wary of a possible backlash when the two teams meet.
According to the PSL, the first leg encounters will be played on the weekend of August 26-27, with the return legs scheduled for the weekend of September 9-10.
The league will announce venues and kick-off times in due course.