Retrofitting existing residential buildings is a critical strategy for achieving urban decarbonization while addressing public health disparities, particularly in communities disproportionately affected by environmental and socioeconomic stressors. This study presents a scalable urban building energy modeling framework that integrates physics-based simulations with machine learning to evaluate and prioritize health-driven retrofit strategies across residential building stocks. Synthetic datasets were generated through parametric simulations of representative building archetypes and retrofit scenarios, capturing variations in envelope performance, HVAC systems, infiltration rates, and ventilation strategies. Machine learning models were trained as surrogate predictors of building energy performance, enabling rapid evaluation of retrofit impacts. A range of algorithms—including decision trees, random decision forests, gradient boosting machines, support vector machines, k-nearest neighbors, and artificial neural networks—were evaluated. An artificial neural network implemented as a multilayer perceptron was selected for further analysis due to its strong predictive performance (R² = 0.94) and ability to capture complex nonlinear relationships among retrofit variables. The final model used the Port optimization algorithm for stable convergence and improved generalization. The framework is applied to Seattle’s Duwamish Valley, a community experiencing disproportionate environmental and health burdens. The results highlight retrofit priorities—particularly infiltration reduction, HVAC upgrades, and improved envelope performance—that deliver co-benefits for energy efficiency, indoor environmental quality, and occupant health. The results demonstrate that machine learning–enhanced physics-based UBEM can significantly accelerate retrofit evaluation while preserving the interpretability of simulation-based approaches. The proposed framework provides a scalable approach for identifying health-informed retrofit pathways that support equitable urban decarbonization.