We report the case of a 54-year-old man with right-lung pneumonia and contralateral pulmonary embolism (PE) conditioning severe refractory hypoxemia requiring veno-venous extracorporeal membrane oxygenation. Electrical impedance tomography (EIT) was used to assess recruitability and regional ventilation and perfusion. At a clinical positive-end expiratory pressure (PEEP) of 12 cmH₂O, EIT revealed predominant ventilation in the left lung and predominant perfusion in the right lung. Reduced perfusion in the left lung raised suspicion of PE, confirmed by contrast-enhanced computed tomography. The clinical PEEP was insufficient to maintain recruitment of the pneumonia-affected right lung, which showed an airway opening pressure (AOP) of 16 cmH₂O. Therefore, PEEP was increased to 20 cmH₂O to exceed the AOP of the injured lung, improving lung recruitment, stabilizing end expiratory lung impedance (EELI), and increasing V/Q matching. Oxygenation improved, following an increased cardiac output, and reduced pulmonary vascular resistance. Despite increasing ventilation pressures, the higher PEEP was well-tolerated hemodynamically, optimizing V/Q coupling in this case of unilateral shunt and contralateral dead space. This case highlights the utility of ventilation/perfusion EIT in optimizing ventilatory strategies, in anticipating the presence of pulmonary malperfusion at bedside, and demonstrating the importance of individualized, physiology-based interventions in complex critical care scenarios.