Shadab led Pakistan during the recently concluded T20I series in the absence of the injured Babar Azam but was rendered unavailable for selection for the first Test in light of his thigh injury.
He was scheduled to undergo MRI scans on Thursday, which confirmed the serious nature of his thigh injury.
Shadab has been "diagnosed with high-grade full thickness tear to the Rectus Femoris muscle", according to the media release issued by the PCB.
He sustained the injury during Pakistan's four-wicket win against New Zealand in the final match of the series, where he conceded 36 runs in his four-over spell and was dismissed for a golden duck.
Shadab will now miss South Africa's first trip to Pakistan in 14 years, comprising of two Test matches and three T20Is set to commence on January 26. Additionally, he will not take part in the Christchurch Test that will be played from January 3-7.
“The MRI reports have confirmed it is a fresh injury and not the one that had sidelined him from the Zimbabwe series last month," said Dr Sohail Saleem, PCB's director of medical and sports sciences.
"The latest injury will be treated conservatively and Shadab will undergo a six-week rehabilitation programme during which he will have weekly ultrasound scans. After the competition of the six-week period, the medical panel will access and evaluate the injury before making a call on Shadab’s return to competitive cricket," he added.
Shadab's injury woes also kept him from participating Pakistan's home assignment against Zimbabwe last month. He was doubtful for the first T20I against New Zealand on December 18 but recovered in time to make his captaincy debut for Pakistan.
The 22-year-old will continue his stay with the Pakistan side in New Zealand and begin his rehabilitation programme under the supervision of the medical team before travelling back home.