Missions have played numerous developmental roles towards the achievement of economic and social advancement including the provision of healthcare. From their entry into Africa, they have employed numerous methods in order to introduce their Christian faith. The construction of schools and hospitals, engagement in public health campaigns, provision of relevant services for the poor, and spearheading the provision of formal education, among others, have been the most effective mechanisms. The activities of missionaries have taken different dimensions as their scope continues to change over time. Nevertheless, existing literature shows little data on the changing landscape of mission medicine and hospitals in Africa. Using a systematic literature review approach, the current study discusses the changing landscape of mission medicine and hospitals in Sub-Saharan Africa. This contribution dwells partly on the missionary theory of medical practice to define most of the services of these faith-based organization (FBOs) in Africa. Findings from the study have revealed that mission hospitals have established schools and training schemes that allow them to train medical personnel to complement the limited number of health personnel on the continent. In the twenty-first century, they have contributed to achieving the targets of the Millennium Development Goals (MDGs) and the Sustainable Development Goals (SDGs), especially aspects that focus on health. It is evident that while the focus, methods, and partnerships have changed, missions in healthcare have not diverted their attention from sharing the gospel of Jesus Christ.