Abstract Background Neonatal pulmonary embolism is a rare occurrence, especially when idiopathic, instead occurring in patients with identifiable risk factors including severe dehydration, presence or history of a central venous line or identifiable genetic causes. Given the rarity of pediatric and neonatal pulmonary emboli, few guidelines exist to support the clinician in both the initial resuscitation and ongoing management of the critically ill patient with pulmonary emboli. Case summary We present a 5-day old with unprovoked massive pulmonary embolism and associated hemodynamic compromise. She presented with central cyanosis and weak respiratory effort with hypoxemia, persistent tachycardia and hypotension despite initial fluid resuscitation, intubation and administration of 100% FiO2 and inhaled nitric oxide. She was ultimately diagnosed with a massive pulmonary embolism involving the right pulmonary artery by both echocardiography and computed chest tomography, initiated on inotropic support and systemic anticoagulation, after which she underwent mechanical thrombectomy. She was successfully extubated soon thereafter, with subsequent resolution of her emboli. No provoking factors were able to be identified for this patient. Discussion This case highlights the cumulative burden of pulmonary obstruction and inter-ventricular interactions that lead to hemodynamic compromise in the event of massive pulmonary embolism, with resultant considerations of key management strategies. These include the risks of fluid resuscitation and introduction of positive pressure ventilation, as well as the need for early consideration of inotropic support and an institutional pathway for anticoagulation, ultimately proposing a multidisciplinary algorithm for the clinician to deploy when faced with impending cardiovascular collapse from massive pulmonary embolism.