The resilience and reliability of healthcare supply chain models were put to the test by the Corona Virus Disease 2019 (COVID-19). This study investigated the application of supply chain systems in South African healthcare institutions during the COVID-19 pandemic. A systematic literature review (SLR) was employed to explore the performance of existing supply chain systems, followed by a case study that tested and compared the acquisition and distribution of COVID-19 resources. The SLR revealed that most of the flare-ups were exacerbated by the acquisition of insufficient resources and speculative shortages as the supply chain systems got overwhelmed by the unprecedented demand. The simulation of the real-world data of South Africa revealed gaps in the distribution of resources, allocation of medical staff to administer COVID-19 vaccines, and shortages of vaccines. The study recommends development of effective contextual (SA) healthcare supply chain systems to support the containment of pandemic flare-ups. The study was conducted in South Africa and only reported data was used.