Rapid urbanization and climate change have exacerbated urban heat stress, underscoring the importance of research on human thermal comfort for sustainable urban development. This study analyzes the spatiotemporal variation and driving factors of apparent temperature in the Chang–Zhu–Tan urban agglomeration, China. The Humidex index, representing apparent temperature, was derived from multi-source remote sensing data (Landsat 8, MODIS) and meteorological variables (ERA5-Land reanalysis), employing atmospheric correction, random forest modeling, and path analysis. The results indicate pronounced spatiotemporal heterogeneity: apparent temperature reached its maximum in urban centers during summer (mean 52.9 °C) and its minimum in winter (mean 5.99 °C), following a decreasing gradient from urban core to periphery. Land cover emerged as a key driver, with vegetation (NDVI, r = −0.938) showing a strong negative correlation and built-up areas (NDBI, r = +0.8) a positive correlation with apparent temperature. Uniquely, in the Chang–Zhu–Tan region’s persistently high humidity, water bodies (MNDWI, r = +0.616) exhibited a positive correlation with apparent temperature, likely due to humidity-enhanced thermal perception in summer and relatively warmer water temperature in winter. Path analysis revealed that air temperature exerts the strongest direct positive influence on apparent temperature, while relative humidity and NDVI primarily act through indirect pathways. These findings provide scientific evidence to guide climate-adaptive urban planning and enhance human living conditions in humid environments.