Recent earthquake disasters have highlighted an urgent need for continuous advancements in approaches to reducing seismic risk. Decision-making on such strategies should consider subsurface geophysical information (e.g., seismic site response), given its direct link to seismic hazard. This may be particularly important in regions where the poorest in society often reside in areas with softer soils that lead to higher ground-motion amplifications. In this context, we propose a framework to support decision-making on earthquake risk policies, which explicitly integrates information on the geophysics of an urban system as well as its physical and social environment. The framework is based on the Tomorrow’s Cities Decision Support Environment, which was designed to support urban planning with a focus on pro-poor disaster risk reduction in countries of the Global South. It is further underpinned by a cost–benefit analysis, which facilitates the assessment of potential policies in terms of both their ability to reduce earthquake risk as well as their value for (often limited) money. We illustrate the framework using a well-established virtual urban testbed based on Global South cities, which reveals that geophysics-informed policy making can successfully lead to pro-poor earthquake risk reduction.