<p>Rapid climate warming is leading to a notable increase in glacier recession and the formation of glacial lakes, which are becoming increasingly characteristic of high mountain regions globally. These severe cryospheric changes critically affect regional water supply, increase geohazards, and threaten lives and livelihoods. This study records regional glaciers and glacial lake dynamics for the period 1990 to 2024, considers the implications of these changes for glacial lake outburst floods (GLOFs) and assesses the potential future flood hazard. Several remotely sensed and reanalysis datasets from 1990 to 2024 are employed to investigate changes in glacier and lake areas. The results highlight a significant reduction in the Manaslu (−0.72±0.20 km²/a) and adjoining glaciers, which led to an increase in the Birendra glacial lake (0.23±0.04 km²/a). Additionally, surface elevation and ice movement data reveal significant thinning of glaciers in the region, averaging −1.52±0.26 m/a, often associated with avalanches near the glacier terminus and triggering GLOFs. Using an HEC-RAS (Hydrologic Engineering Center’s River Analysis System) model, a total extension of 19.3 km of flow channels was revealed, coupled with potential increases in depth, discharge, and velocity, potentially causing massive damage downstream. Regional hazard intensity assessment indicates that five bridges, 31 houses, and 1.2 km² of agricultural land may be flooded, with the more populated areas near Samagaun and Banjam being the most affected. Regional climate condition, including significant rising air temperature (0.02°C/a, <i>p</i>&lt;0.05) and declining precipitation (−0.24 mm/a, <i>p</i>&lt;0.05), during recent decades play a crucial role in glacier dynamics and exhibit a significant spatial relation with increased temperature (<i>R</i>² = 0.62, α &lt;0.05). Understanding regional cryospheric dynamics and associated risks is therefore essential in designing adaptive mitigation strategies.</p>