The duo were originally named in Hector Cuper’s 25-man team for the final matchday away encounter set for the Cape Coast Sports Stadium.
Al Ahli left-back Abdel-Shafy was the first to pull out.
Announced by the Egyptian Football Association on Monday, national team doctor Mohamed Abou El-Ela revealed the Saudi Arabia-based full back needs a week to resume training after picking up an injury on club duty, effectively ruling him out of Sunday’s fixture.
It will be the Pharaohs’ first game of the last round qualifiers without the 32-year-old, who has featured in all five previous matches.
West Bromwich Albion centre-back Hegazi is the latest to withdraw from the Ghana trip.
The EFA has announced the 26-year-old has left the national camp due to family reasons.
Egypt will also be without talisman Mohamed Salah, who failed to make Cuper’s 25-man squad altogether, having been excused to avoid burnout.
The Pharaohs have nothing but pride to lose should they fail to pick a good result on Sunday, having already sealed qualification to Russia 2018.
On their last visit to Ghana, the Pharaohs were handed a 6-1 thrashing by the Black Stars in a 2014 World Cup qualifier in Kumasi in 2013.