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Background: Natural disasters and pandemics can be highly challenging to blood supply chains. This review aimed to assess the impacts of pandemics and natural disasters on blood donation globally, appraise any similarities and differences, and provide an overview of the mitigation strategies and optimizations applied as well as risks modelling undertaken. Methods: Full text, peer-reviewed articles that studied the impact of any pandemic and natural disaster on blood donation, blood supply management, and modelling searchable in PubMed, Scopus, Web of Science, and Cochrane Library between Jan 1980 and Jan 2023, inclusive were included. We performed quality assessments and summarised potential lessons learned. Results: Overall, 98 studies were identified and assessed in this review, of which 58 were related to pandemics and 17 related to natural disasters. 97% of the studies on pandemics and blood donation were on COVID-19, while 88% of studies on natural disasters were on earthquakes. We confirmed that during the COVID-19 pandemic, blood donation numbers decreased compared to the pre-pandemic period, while just after an earthquake, blood donation numbers tended to increase, which in both cases put the blood supply chain under pressure (creating shortage or wastage). The increase of first-time donors was higher after a sudden destructive earthquake than after the COVID-19 pandemic. Public awareness campaigns, donors transportation, home visits, measures to minimize wastage of blood components, activation of contingency plans, and altering donor eligibility criteria were implemented to help the blood supply chain to respond to the demand and reduce wastage. However, no pandemic plans, per se were identified highlighting the lack of an emergency plan in collaboration with health authorities. Several optimization models were developed to help the blood supply chain reduce costs and identify faster transportation in times of earthquake, however, optimization models targeting a pandemic were lacking, as were risk modelling analyses for both events. Conclusion: Optimization models, risk modelling, serosurveillance and haemovigilance should be combined with infectious diseases case surveillance to better prepare the whole supply chain logistics to safely attend the demand. Findings on blood donor demographics were inconclusive during or after major events, which highlight the need for further investigations.