Expanding sanitary sewer networks is vital for meeting the Sustainable Development Goals (SDGs) for urban areas. Uncertain future design conditions threaten this infrastructure expansion; notably, climate change has been described as the biggest threat to achieving the SDGs. However, the literature on how climate change can affect sanitation is sparse, especially in low- and middle-income countries, where infrastructure is most needed. We created a simple hydraulic model that quantitatively examines how the uncertainty-induced threats related to urbanization, stormwater inflow, and climate change might affect designed sanitary sewers. Our sanitary sewer model allows a designer or operator to estimate how urban development (e.g., population growth, water consumption, and expansion of impervious areas), stormwater infow, or changing rainfall patterns (e.g., climate change scenarios) would affect the performance of a sanitary sewer network. We identified that the fraction of stormwater inflow entering the sanitary sewers is the most significant threat to urban sewers. Applying the model to three case studies in Brazil revealed that the fraction of stormwater inflow in sanitary sewers is at least 1.8 times more influential than the other considered uncertainties. Stormwater inflow collected in the sanitary system leaves the network vulnerable to extreme rainfall events, consequently leaving the design guidelines vulnerable to climate change, which may compromise their ability to achieve the SDGs. Our model quantitatively demonstrates the essential role that minimizing inflow must play in ensuring climate resilient sanitation and in maximizing the utilization of sanitary sewers. Safely managing human waste is critical to the health and well-being of humans, especially in cities. Investments in resilient sanitation infrastructure can generate a significant return on investment in health-related benefits. However, if not accounted for, climate change effects can compromise the ability to provide safe sanitation. While 3.5 billion people still need sanitation infrastructure today, methods of expanding sewer systems amid climate change are unclear. In this paper, we provided a simple model that gives a designer or operator insights into the implications of how various sources of uncertainty (urbanization, stormwater inflow, and climate change) can affect the performance of sanitary sewers. Applying the proposed model to three regional capital cities in Brazil, we demonstrated that the biggest threat to urban sewers, even compared to urbanization and climate change, is the fraction of stormwater entering a sanitary sewer. When building or expanding sanitary sewers, inaccurate estimates of how much stormwater will enter the sanitary system can lead to sewage overflow, which might result in health, environmental, and economic hazards. Minimizing the fraction of stormwater that enters the sanitary system would increase the resilience of the sewer network against extreme rainfall events that would increase due to climate change.