Ismaili, desperately needing a win to boost their hopes of reaching the Champions League semi final, threw away their lead to lose 2-1 at Nigeria's Heartland on Sunday.
The Egyptian coastal side went ahead after 31 minutes, thanks to a goal from skipper Mohamed Hommos.
ThankGod Ike brought Heartland level shortly before the break and substitute Chinedu Efugh notched home from close range with five minutes remaining to give Heartland their first group-stage win.
Ismaili, whose players were fasting during the 19th day of Muslims' holy month of Ramadan, struggled to move the ball around on a muddy pitch.
They were also made to pay for their unadventurous display which allowed Heartland to have the upper hand.
Heartland leapfrogged Ismaili into third place in Group B with four points, leaving their opponents, who have three points, at the bottom with two matches remaining.
JS Kabylie of Algeria, who top the group with maximum nine points, take on second-placed Ahli, who have four points, later on Sunday.
The group winners and runners-up will qualify for the semi final of Africa's premier club competition.
Cautious IsmailiIsmaili were cautious in the early stages of the game, allowing Heartland to lay siege to their area.
Dutch coach Mark Wotte fielded three defensive midfielders in Ismaili's starting line-up but they were incapable of closing down spaces as Heartland threatened keeper Mohamed Sobhi on a couple of occasions.
Sobhi, who regained his regular place between the sticks after Essam Al-Hadari joined Zamalek in the off-season, dived to his right to block a low shot from Ikechukwu Ibenegbu at his near post after 16 minutes.
Ismaili were cautious in the early stages of the game, allowing Heartland to lay siege to their area.
Dutch coach Mark Wotte fielded three defensive midfielders in Ismaili's starting line-up but they were incapable of closing down spaces as Heartland threatened keeper Mohamed Sobhi on a couple of occasions.
Sobhi, who regained his regular place between the sticks after Essam Al-Hadari joined Zamalek in the off-season, dived to his right to block a low shot from Ikechukwu Ibenegbu at his near post after 16 minutes.
Abou-Greisha's introduction did not make differenceHe also palmed a powerful shot from Chibuzor Ozurumba 12 minutes later.
Ismaili opened the scoring against the run of play after exploiting the gaps in Heartland's defense in the 31st minute.
Hommos timed his run to perfection to break the offside trap and control a long ball inside the area before slotting home with aplomb.
Despite taking the lead, Ismaili still appeared shaky at the back and Heartland punished their slack defending to level the score on 40 minutes.
Joshua Obaje, who was unmarked at the far post, headed a cross into the path of Ike to send a low shot past Sobhi from inside the area.
Natural winger Ahmed Samir Farag switched to the back in the second half to help Ismaili's defense withstand sustained pressure from Heartland but the tactical change did the Dervishes no favor.
Sobhi, who produced an outstanding display, once again thwarted a dangerous effort from the hosts when he saved John Owoeri's shot from a tight angle five minutes past the hour mark.
Wotte introduced strikers Mohsen Abou-Greisha and Abdessalam Benjelloun instead of misfiring duo Ahmed Ali and Godwin Ndubuisi but they failed to muster a shot on goal.
Heartland maintained their dominance as Ismaili needed a brilliant reflex save from Sobhi to deny Emmanuel Omodiagbe on 80 minutes.
The Nigerian made amends five minutes later to claim all three points and dent Ismaili's hopes of booking a last-four berth for the first time in seven years.
A corner was flicked into the path of Efugh at the far post and he made no mistake from two yards out despite being under pressure from an Ismaili defender.