Urban human thermal stress can be inaccurately estimated along with less-understood heat heterogeneity due to the absence of high-resolution meteorological information and realistic human behavior representation. To this end, we coupled a regional climate model (weather research and forecasting model, WRF) and a human energy balance model (human-environment adaptive thermal stress model, HEATS) to predict pedestrian's dynamic thermal stress at a neighborhood scale. The WRF-human coupling system resolves human-environment heat exchanges based on meteorological and topographical information with the consideration of dynamic human activities. The coupling system has been tested and utilized to study dynamic heat stress in a typical hot, humid, and mountainous city, Hong Kong. Our results revealed widespread heat heterogeneity with up to 7 °C difference in Physiological Subjective Temperature (PST) in the core urban area, and extreme heat exposure (up to 45 °C PST) in calm-wind zones at noon. Heat stress can be further aggregated considering realistic human behaviors such as extra clothing (e.g., protective facemask during pandemics) and physical exercise (e.g., walking along inclined terrain). Optimal-thermal-comfort routes have been designed and suggested based on the simulated neighborhood-scale heat stress map.