Background: The World Health Organization (WHO) South-East Asia (SEA) Region comprises over 2.1 billion people and faces rapidly increasing demand for platelet transfusions due to rising trauma, hematologic malignancies, complex surgeries, and recurring dengue epidemics. Despite substantial progress, platelet transfusion practices across SEA remain heterogeneous, influenced by variations in health-system capacity, regulatory maturity, and geographical constraints. Objective: This review summarizes the historical progression, current practices, safety mechanisms, clinical utilization patterns, and future opportunities in platelet transfusion across SEA. Summary: Platelet transfusion in SEA has evolved from early manual platelet-rich plasma preparation in the 1950s to widespread use of component therapy, including random-donor pooled platelets and single-donor aphaeresis platelets (SDAP). Countries such as Singapore, Sri Lanka, and Thailand have achieved significant milestones through universal leucodepletion, nucleic acid testing (NAT), strengthened hemovigilance systems, and pilot implementation of pathogen inactivation (PI) technologies. However, many nations continue to face challenges, including inconsistent donor availability, high dependence on pooled platelets, limited apheresis capacity, and fragmented regulatory oversight. Seasonal dengue outbreaks remain a major utilization driver despite strong evidence discouraging prophylactic transfusions in non-bleeding dengue patients. Expanding transplant programs, maternal hemorrhage, and critical care needs further contribute to increased demand. Emerging innovations—such as cold-stored platelets, platelet additive solutions (PAS), digital blood-bank management platforms, and genomic matching—offer promising avenues to improve safety, efficiency, and sustainability. Conclusion: Achieving equitable, safe, and evidence-based platelet transfusion services in SEA requires harmonized guidelines, expanded apheresis infrastructure, robust hemovigilance, integration of PI technologies, and strengthened regional collaboration.