Health systems in Ghana have faced numerous challenges during epidemic responses, necessitating a theoretical framework to understand resilience. This article employs qualitative analysis of existing literature on health systems resilience and epidemic response in Africa, focusing specifically on Ghanaian experiences. The theoretical model underscores the importance of integrating local knowledge and resources into health systems for effective epidemic management. Future research should focus on developing targeted interventions based on this framework to improve Ghana's health systems' resilience in future epidemic responses.