Non-communicable diseases (NCDs) are rising rapidly in urbanizing populations in sub-Saharan Africa. Assessment of inflammatory and metabolic characteristics of a urbanizing African population and the comparison with populations outside Africa could provide insight in the pathophysiology of the rapidly increasing epidemic of NCDs, including the role of environmental and dietary changes. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we examined differences in the inflammatory proteome in healthy Tanzanian and healthy Dutch adults. We show that healthy Tanzanians display a pro-inflammatory phenotype compared to Dutch subjects, with enhanced activity of the Wnt/b-catenin signalling pathway and higher concentrations of different metabolic regulators such as 4E-BP1 and fibroblast growth factor 21. Among the Tanzanian volunteers, food-derived metabolites were identified as an important driver of variation in inflammation-related molecules, emphasizing the potential importance of lifestyle changes. These findings endorse the importance of the current dietary transition and the inclusion of underrepresented populations in systems immunology studies.