Mental Health and Psychosocial Support is a growing field of intervention in humanitarian assistance worldwide. The influence of culture and faith in individual and collective coping mechanisms and recovery processes has brought scholars to emphasize the need for MHPSS programming to adopt a cultural and faith sensitive approach to increase the cultural relevance and efficacity of interventions. However, despite official guidelines for humanitarian agencies to integrate cultural and faith sensitivity in their operations, there is an information gap on designing such an approach and its effects on the implementation and success of interventions. This qualitative study explores the opportunities and challenges encountered when adopting a cultural and faith sensitive approach within MHPSS interventions in the context of the Red Cross in Zambia, Ghana, Niger, and South Africa. Based on in-depth interviews with key informants from the Red Cross, the results provide insights into the strengths and opportunities of adapting to local cultural norms and practices and cooperating with faith-based and traditional community leaders during the implementation of MHPSS. The study concludes on the potential of such an approach to strengthen the local capacities of faith-based actors and reduce the stigmatization of mental illness.