Acute transfusion reactions (ATRs) in children represent a heterogeneous group of allergic, immunologic, and non-immunologic events that can be life-threatening and clinically indistinguishable, particularly in immunocompromised cohorts. This case-based narrative review explores the spectrum of pediatric ATRs, focusing on pathophysiological mechanisms, diagnostic hurdles, and management strategies. The discussion is framed by two pediatric cases involving four distinct ATRs: first, a child with DOCK8 deficiency undergoing hematopoietic stem cell transplantation who experienced urticaria and subsequent anaphylaxis due to suspected passive allergen transfer; and second, a child with malignancy who developed febrile non-hemolytic and acute hemolytic reactions despite ABO compatibility. These scenarios are analyzed alongside critical entities such as transfusion-associated circulatory overload (TACO) and transfusionrelated acute lung injury (TRALI). This review underscores the need for heightened clinical vigilance and highlights passive allergen transfer as an increasingly recognized mechanism essential to enhancing pediatric transfusion safety.