Stellies secured their last four place with a 1-0 aggregate victory over Egyptian giants and defending champions Zamalek.
Fadlu Davids' Simba, meanwhile, overcame Egyptian side Al Masry 4-1 on penalties after their quarter-final ended in a 2-2 stalemate after two games.
While Steve Barker's team are in third place on the Betway Premiership standings, Simba are in second spot on the Tanzanian Premier League table.
Both teams come into this game in some good form, while Stellenbosch have been boosted with the return of goalkeeper amd captain Sage Stephens after his absence in the 1-0 league win over AmaZulu due to injury.
Ahead of the game, Barker said on FARPost: "I saw Sage and had a little bit of follow-up [about the injury progress after the AmaZulu game]. The reason he didn’t play [against AmaZulu FC] was to let him recover fully. But he seems to be good.
"So, he will travel with the team. I'm confident that by the weekend, he will be available. He seems to have recovered from the injury. He has been big for us this whole season, and it's important for him to be available."
Davids knows Stellenbosch all too well from his time in South Africa and has praised the Cape-Winelands club, saying they are one of the best teams they can expect to face in the competition this season.
“Already, of course, we know Stellenbosch well. We've played against them many times, as a technical team. We know how good a side they are and give them huge respect. They are probably the best team we've played so far in CAF,” he said.
"Speed, fitness, intensity, they will match us. We require a very, very good performance to get a good result in the first-leg."
The first leg takes place at the New Amaan Complex in Zanzibar, as SImba's their home stadium is currently under repair.