Zamalek need a win this weekend and a favour from fellow Cairo club Al Ahly to have any chance of surviving the African Champions League group phase.
Victories for the two Egyptian sides would give their rivals Ahly an unassailable eight-point lead in Group B and bring Zamalek back into contention for second place.
In Group A, defending champions Esperance have a five point advantage over fellow Tunisian side Etoile Du Sahel. The pair will meet at the Stade Olympique d'El Menzah.
The top two teams in the each group qualify for the semi-finals.
Pointless Zamalek will entertain TP Mazembe from the Democratic Republic of Congo, behind closed doors as a result of security concerns, while Ahly are away to third-placed Berekum Chelsea in Ghana.
Mazembe defeated Zamalek 2-0 at home two weeks ago, while a Walid Soliman brace clinched a 4-1 triumph for Ahly over Chelsea in Cairo.
A hat-trick of victories leaves record six-time African champions Ahly on nine points, Mazembe and Chelsea are separated by goal difference as they have four points each and Zamalek have suffered three consecutive losses.
But Egyptian victories in Cairo and Accra would move Zamalek within one point of Mazembe and Chelsea and open up the race to finish runners-up in the so-called group of death.