Synthetic Biology is a powerful technology, capable of creating low cost, effective healthcare solutions (e.g. drugs and molecular diagnostics) that could be used in extremely impoverished regions of the world. While the potential impact of Synthetic Biology, in general, is compelling, two challenges have limited this impact to date: (1) the identification of specific opportunities remains challenging, as the vast majority of Synthetic Biology practitioners live far away from the resource-poor and are not intimately aware of the problems, and (2) adequate early and mid-stage funding to pursue problem-specific technologies. Significant advancement could be made by sending Synthetic Biology observational teams to resource-poor locations, and based on their observational research and Synthetic Biology expertise, develop problem-specific research plans that can be executed with in-country collaborators. The problem-first approach described in this plan aims to maximize impact by focusing resources on well-formulated matches between healthcare problems and appropriate Synthetic Biology technologies.