The Cairo club shocked Esperance in Tunis last weekend, coming from behind to triumph 2-1 through goals from Tunisian Ali Maaloul and Nigerian Junior Ajayi.
Now, 2007 champions Etoile Sahel hope to succeed where Esperance failed, and enjoy semi-final home advantage first at Stade Olympique in Mediterranean resort Sousse.
The clubs have clashed twice in Champions League finals with Ahly winning 3-0 overall in 2005 and Sahel turning the tables two years later with a stunning 3-1 success.
This century, Ahly have never gone four years without lifting the Champions League trophy that symbolises African club supremacy.
With the last of eight titles won in 2013, the "Red Devils" are under pressure from supporters to go all the way this season.
"Our fantastic fans are demanding that we win the Champions League this year," admitted coach and former Ahly star Hossam el Badry.
"They want a ninth star on our shirts and a chance to compete against the best at the FIFA Club World Cup.
"Our target is winning the Champions League this year -- nothing less," stressed the 57-year-old in his third spell as Ahly coach.
CAF Champions League winners wear shirts with a star for each title above the club badge.
An Egyptian with Etoile and a Tunisian at Ahly could play key roles in the semi-final.
Sahel promoted Egyptian Amr Marey in place of banned Brazilian Diogo Acosta and he rewarded French coach Hubert Velud with a brace in the 2-0 home win over Al Ahly Tripoli of Libya.
Tunisian Maaloul is an experienced CAF campaigner and a left-back with a licence to roam, whose goal set up the downfall of Esperance.
On Friday, USM Alger of Algeria host Wydad Casablanca of Morocco in the other first leg of a competition that has become an exclusively north African affair at the last-four stage.
Both clubs were Champions League runners-up this decade -- USM to TP Mazembe of the Democratic Republic of Congo in 2015 and Wydad to Esperance four years earlier.
USM disappointed last weekend, only drawing 0-0 at home to lightweights Ferroviario Beira of Mozambique and squeezing through on away goals.
Much more will be expected of leading scorer Oussama Darfalou against Wydad, who won the competition in 1992 when called the African Cup of Champions Clubs.
The Casablanca outfit have lost four of five away matches, but eliminated title-holders Mamelodi Sundowns of South Africa to reach the semi-finals.