This research explores the determinants of hospital emergency preparedness in the Ashanti Region of Ghana using a cross-sectional design. A convenience sampling method was used to select 360 health professionals. Data was collected using a structured questionnaire. The Statistical Package for Social Sciences (SPSS) Version 26.0 was used to analyze the data collected. After analyzing the data, the study revealed that the capacity of healthcare professionals played an essential role in hospital emergency preparedness. The capacity in which health professionals play a role in hospital emergency preparedness promotes primary health and prevents illness, enhances the day-to-day operation and readiness for emergency cases, and ensures access to quality health care. It was recognized that the factors that influence the determinants of hospital emergency preparedness were financial capacity or funding, top management decisions on emergency preparedness, infrastructure availability, hospital resource management, plan strategy or tool for hospital emergency preparedness, and hospital communication and triage system. The study established that the challenges of hospital emergency preparedness were inadequate staff or health professionals, improper management, lack of education and training drills on emergency preparedness management, inadequate finance, lack of necessary healthcare facilities and equipment, poor surveillance systems, inadequate resource capability, and lack of laid down plan or strategy for emergencies. It was recommended that training drills must be conducted regularly. Also, healthcare professionals should be informed about the training programs, and the hospital management should ensure that all plans and policies are maintained and updated regularly.