The increasing concern related to radiological and nuclear threats within the European Union (EU) has intensified the regional preparedness needs. The anticipated number of injured, contaminated, and irradiated individuals may range from a few to hundreds of thousands, necessitating immediate emergency medical care and hospitalization. Given this potential influx of casualties, the medical teams responsible for initial management may become rapidly overwhelmed, facing immense pressure to formulate appropriate response strategies and treatment options. Therefore, it is critical to establish appropriate supra-national recommendations and appropriate national protocols to guide medical decision-making in such extraordinary circumstances. The EU is proactively preparing for this worst-case scenario. Drawing on a robust and remaining state-of-the-art reference consensus regarding the medical management of mass radiation exposure, a well-established network of 550 European Society for Bone and Marrow Transplantation (EBMT) centers and emergency medicine specialists, and two decades of collective experience in managing acute radiation syndrome (ARS) patients. The European Commission (EC), in collaboration with the World Health Organization (WHO) Europe, is accelerating the dissemination of medical response protocols. This initiative includes the education of healthcare professionals and the implementation of a strategic stockpile of medical countermeasures to address nuclear-related threats effectively.