Hossam Hassan's side were dramatically denied at Harras Hodoud in the opener as they face an opponent who were off to a losing start at home.
The corresponding fixture last season, ironically in week 2 as well, resulted in a crucial defeat to Zamalek in Cairo.
This time Petrojet boss Helmi Toulan, a former Zamalek coach, vows to cause another upset and claim his first points with the Suez club.
"We lost the first game against Ismaili but the new formation (4-4-2) was a success," said Toulan, who took over from Mokhtar Mokhtar in the summer.
"The game is important, yet difficult for us. But I'm confident the players can play well against Zamalek and bring home the first win."
Team news
Zamalek enter the game amid various squad problems involving top players like Shikabala, Hussein Yasser and Amr Zaki.
Star playmaker Shikabala is the subject of a controversial transfer story with Anderlecht, while Qatari forward Yasser returned late from international duty and has been promised a 'severe sanction' by the Zamalek management.
However, the duo were named in the match squad, along with Zaki who is once again struggling with injury following an impressive pre-season.
Meanwhile, Hassan Mostafa and Ahmed Ghanem were ruled out, but Hani Saied is fit again and Hazem Emam is back from a long suspension.
As for the visitors, first-choice keeper Ahmed Fawzi has been ruled out with injury as youngster Mohamed Al-Beshbishi is set to step in.
Elsewhere, newly-promoted pair MCDR and Wadi Degla lock horns, following the latter's incredible Egyptian league debut last week.
After thrashing Arab Contractors 4-1 at home in the opener, Degla sent a clear message they will not be just fighting against relegation this term.