Pat Cummins' side will deal with a pitch offering little bounce and plenty of turn when they begin their chase on Saturday, with the series firmly on the line.
Simon Harmer looms as the main threat after taking 4-104 in the first innings, after also spinning South Africa to victory over India on a dry pitch in Guwahati last year.
Marques Ackerman could also bowl some wrist spin after warming up before play on day four, while Aiden Markram has also offered some tweakers.
But one thing South Africa believe could play into Australia's favour is their left-handers.
The majority of rough and footmarks at Newlands this week have been outside the right-hander's off stump, making it a target for Nathan Lyon on Friday.
He caused particular trouble for right-hander Matthew Breetzke and bowled fellow right-hander Harmer, while Ryan Rickelton had less issue on his way to 101.
"It was a lot easier for me, there wasn't a lot of turn off the straight yet," Rickelton said of facing spin in the conditions.
"But for the right-handers the ball is vicious coming back in."
Both Australian openers, Travis Head and Matt Renshaw, are left-handers, along with Alex Carey and Cooper Connolly. No.9 Mitchell Starc also fits the bill.
"We know Australia has four left-handers (in their top seven), we're going to look to put them under pressure," Rickelton said.
"Whether it be hanging it out there and waiting for them to come to us, or attacking it differently in their own personal styles.
"We know we have our work cut out for us tomorrow. But when the right-handers are in obviously there is a lot of action for them."
One challenge Rickelton does see for Australia with the pitch on Saturday is a lack of pace.
Albeit with the Proteas happy to take up time for the match situation on Friday, they went at less than three an over in their second innings with the ball not coming onto the bat.
Australia will need to score at 3.2 an over to chase down the 288, with both teams set to initially pursue a win on day five rather try to protect a draw.
"With that new ball there is obviously runs available and obviously wickets too," Rickelton said.
"It definitely felt like it was quite slow (after that), and the ball was soft as well so to beat the infield was quite hard.
"If Australia decide to have a go at it, (the pitch) might factor how they go about it.
"It was a bit two-paced with the bounce, we didn't see too many balls stay low ... for them to bat effectively at three (an over) the whole day will be a big ask."
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