<p>Groundwater serves as the main supply source of water for domestic, drinking, industrial, and agricultural uses. This study assessed the groundwater quality and associated health risks in the Kathmandu Valley. In total, 401 groundwater samples from Lalitpur (299), Kathmandu (82), and Bhaktapur districts (40) were collected from 14th April 2022 to 13th April 2023. The water quality parameters, including pH, electrical conductivity (EC), turbidity (Tur), total hardness (TH), chloride (Cl), nitrate (NO₃⁻), ammonia (NH₄⁺), and iron (Fe) were analyzed. Groundwater quality index, spatial analysis techniques including geographic information systems (GIS), multivariate analysis, and machine learning approach by self-organizing maps (SOM) with hierarchical clustering analysis were employed to identify areas of concern. The results revealed elevated levels of turbidity, NH₄⁺, and Fe in several regions, particularly in urban and semi-urban areas. The nitrate pollution index (NPI) and ammonia pollution index (API) analyses revealed 0.99% and 31.42% of high nitrate and ammonia pollution, respectively. Health risk assessment indicated potential risks, especially for infants, due to exposure to nitrate and ammonia. Principal component analysis (PCA) primarily demonstrated the ion concentration and mineralization, which are affected by both natural geological processes and anthropogenic activities. The groundwater samples were grouped into five clusters using hierarchical clustering after SOM classification highlighted the areas affected by NH₄⁺ and Fe. The study highlights the need for effective groundwater management strategies to mitigate groundwater contamination and protect public health in the Kathmandu Valley.</p>