Structural risk-mitigation measures have been shown to significantly reduce earthquake-induced physical damage and casualties in various regions worldwide. However, these benefits remain unknown or inadequately quantified for potential future events in some hazard-prone areas such as Kathmandu Valley, Nepal, which this article addresses. The analysis involves modeling an earthquake scenario similar to the 2015 Gorkha earthquake (moment magnitude 7.8) and using four exposure inventories representing the current (2021) urban system or near-future (2031) development trajectories that Kathmandu Valley could experience. The results predict substantial losses (€8.2 billion in repair/reconstruction costs and 89,199 fatalities) in 2021 if the building stock’s quality is assumed to have remained the same as in 2011 (Scenario A). However, a partial improvement of the building stock’s quality in the present (Scenario B) can decrease financial losses and fatalities by 17% and 44%, respectively. Moreover, under a “no change” pathway for 2031 (Scenario C), where the quality of the expanding building stock remains the same as in 2011, and the number of buildings is larger to reflect population growth, financial losses and fatalities will increase by 20% and 25% respectively over those of Scenario A. In contrast, further upgrades to the building stock’s quality by 2031 (Scenario D) would reduce financial and human losses by 14% and 54% respectively, relative to those of Scenario A. In addition, the largest financial and human losses computed in the four scenarios are consistently associated with the low- and middle-income population. The main findings of this article can be used to inform decision makers about the benefits of investing in forward-looking seismic risk-mitigation efforts.