Background: The management of Out-of-Hospital Cardiac Arrest (OHCA) remains challenging and controversial due to its poor prognosis. Once resuscitation efforts are initiated, determining whether to continue or terminate the process is difficult, even with established Termination of Resuscitation (TOR) guidelines. Additionally, managing Post-Cardiac Arrest Syndrome (PCAS) complicates care, as it involves addressing ischemic injury, organ dysfunction, and inflammatory responses. These challenges emphasize the need for tailored decision-making to optimize patient outcomes. Case: We report a case of prolonged Out-of-Hospital Cardiac Arrest (OHCA) in a 60-year-old male with end-stage renal disease and diabetes mellitus. Despite a resuscitation time of 410 minutes, the patient achieved return of spontaneous circulation (ROSC) following timely intervention with extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Hyperkalemia and hyperglycemia were identified as contributing factors to the prolonged arrest. After successful resuscitation and management of Post-Cardiac Arrest Syndrome (PCAS), including inflammatory modulation and targeted therapies, the patient made a full neurological recovery (CPC 1) and was discharged without any organ dysfunction typically associated with cardiac arrest. Conclusion: This case highlights the challenges of managing OHCA and offers key lessons. In cases with early bystander CPR, timely ECMO use can address reversible causes of cardiac arrest, showing that even with prolonged resuscitation, favorable outcomes are possible. Given the complex and often multifactorial nature of cardiac arrest, a comprehensive approach is essential. In managing PCAS, inflammatory modulation can be considered as a valuable complement to traditional supportive care. Finally, when standard treatments may introduce complications, a cautious approach is necessary. Further studies are needed to define optimal strategies for managing complex OHCA cases.