To address the limitations of current urban building energy modeling (UBEM), which often neglects moisture effects, we developed a comprehensive roadmap for modeling urban heat and moisture flows. This effort included developing an urban-scale whole-building heat and moisture transfer (HAMT) model that considers wind-driven rain, integrated with a microclimate model known as Urban Weather Generator (UWG). The proposed model was validated through analytical and comparative cases of whole-building hygrothermal performance analyses from the Annex 41 Project. The integrated whole-building and microclimate HAMT models were applied to a real urban building to assess the impact of moisture on annual energy predictions in a hot-humid region of Shanghai. The results show that incorporating moisture effects into the UBEM increases the annual cooling energy demand by 22.11% (5.92% owing to latent heat loads) and the annual heating loads by 6.06%, resulting in a 19.73% increase in the total annual energy loads. Additionally, the outer wall surface temperature decreases during and after rainfall events, with maximum decreases of 3.23 °C in winter and 8.80 °C in summer. Therefore, integrating moisture effects into UBEM is crucial, particularly in humid regions.