Public health benefits are often a key political driver of urban sanitation investment in developing countries, however, pathogen flows are rarely taken systematically into account in sanitation investment choices. While several tools and approaches on sanitation and health risks have recently been developed, this research identified gaps in their ability to predict faecal pathogen flows, to relate exposure risks to the existing sanitation services, and to compare expected impacts of improvements. This paper outlines a conceptual approach that links faecal waste discharge patterns with potential pathogen exposure pathways to quantitatively compare urban sanitation improvement options. An illustrative application of the approach is presented, using a spreadsheet-based model to compare the relative effect on disability-adjusted life years of six sanitation improvement options for a hypothetical urban situation. The approach includes consideration of the persistence or removal of different pathogen classes in different environments; recognition of multiple interconnected sludge and effluent pathways, and of multiple potential sites for exposure; and use of quantitative microbial risk assessment to support prediction of relative health risks for each option. This research provides a step forward in applying current knowledge to better consider public health, alongside environmental and other objectives, in urban sanitation decision making. Further empirical research in specific locations is now required to refine the approach and address data gaps.