We present a case of massive pulmonary arterial thrombosis that occurred in an infant, during the early postoperative period after complete surgical repair of a severe form of Tetralogy of Fallot. The patient required emergent circulatory support with veno-arterial extracorporeal membrane oxygenation immediately followed by percutaneous thrombus fragmentation and local thrombolysis, which enabled partial thrombus removal and hemodynamic stabilization. Subsequently, the patient was scheduled for urgent surgical thrombectomy and central pulmonary arterial enlargement plasty, with successive circulatory and clinical improvement. The etiology of this complication was suspected to be multifactorial; multiple surgeries, systemic inflammatory state, hypoplastic pulmonary arteries, and moderate prothrombotic state. A multidisciplinary collaboration between intensivists, cardiologists, and cardiac surgeons and a rationale and step-by-step clinical approach were paramount to face this rare life-threatening complication.