OBJECTIVES: In responding to a Chemical, Biological, Radiological, and Nuclear explosive (CBRNe) disaster, clinical leaders have important decision-making responsibilities which include implementing hospital disaster protocols or incident command systems, managing staffing, and allocating resources. Despite emergency care clinical leaders' integral role, there is minimal literature regarding the strategies they may use during CBRNe disasters. The aim of this study was to explore emergency care clinical leaders' strategies related to managing patients following a CBRNe disaster. METHODS: Focus groups across 5 tertiary hospitals and 1 rural hospital in Queensland, Australia. Thirty-six hospital clinical leaders from the 6 study sites crucial to hospital disaster response participated in 6 focus groups undertaken between February and May 2021 that explored strategies and decision making to optimize patient care following a CBRNe disaster. RESULTS: Analysis revealed the use of rehearsals, adopting new models of care, enacting current surge management processes, and applying organization lessons were facilitating strategies. Barriers to management were identified, including resource constraints and sites operating over capacity. CONCLUSIONS: Enhanced education and training of clinical leaders, flexible models of care, and existing established processes and tested frameworks could strengthen a hospital's response when managing patients following a CBRNe disaster.