The Central African Region is an agricultural and fishing-based economy, with 40% of the population living in rural communities. The negative impacts of climate change have caused economic/health-related adverse impacts and food insecurity. This original article aims to research four key themes: (i) acute food insecurity (AFI); (ii) childhood malnutrition and mortality; (iii) infectious disease burden; and (iv) drought and mean temperature projections throughout the twenty-first century. Food insecurity was mapped in Central Africa based on the Integrated Food Security Phase Classification (IPC) for AFI. The global hunger index (GHI) was presented along with the proportion of children with undernourishment, stunting, wasting, and mortality. Data for infectious disease burden was computed by assessing the adjusted rate of change (AROC) of mortality due to diarrhea among children and the burden of death rates due to pneumonia across all age groups. Finally, the mean drought index was computed through the year 2100. This population-based study identifies high levels of hunger across a majority of the countries, with the mean drought index suggesting extreme ends of wet and dry days and an overall rise of 1–3 °C. This study is a source of evidence for stakeholders, policymakers, and the population residing in Central Africa.