The present study estimates spatial and temporal (seasonal/annual) trends in daytime land surface temperature (LST) and its drivers (elevation, cloud fraction (CF), atmospheric water vapor (AWV), normalized difference vegetation index (NDVI), and snow cover area (SCA)) over the High Mountain Asia (HMA) during 2001–2019 using MODIS remote sensing data. The findings of the study showed mixed trends in LST in the region with intra-regional variations. Overall, the warming in the region is attributed to increasing AWV and NDVI and declining CF and SCA. The study also found evidence of elevation-dependent warming (EDW) (4500–5500 m AMSL) in some regions. However, the same conclusion cannot be drawn in all the sub-regions of HMA, suggesting the need to explore the effects of additional natural and anthropogenic factors on LST with fine resolution data to improve the understanding of its spatio-temporal dynamics.