This case report discusses a pediatric patient with heparin-induced DRESS Syndrome managed successfully during cardiovascular bypass surgery. An 11-year-old with native aortic valve endocarditis developed DRESS after receiving unfractionated heparin. The syndrome, characterized by fever, eosinophilia, and a pruritic rash, was initially managed with corticosteroids. A subsequent episode prompted a shift to bivalirudin and fondaparinux, avoiding further complications and stabilizing the patient’s condition. This case emphasizes the need for alternative anticoagulation strategies in hypersensitive patients to improve outcomes.