<p>Transboundary water pollution is a pressing global concern due to the cross-border movement of contaminants and the limited exchange of monitoring data between nations. According to the Sustainable Development Report 2022, only 32 countries manage 90% of the transboundary waters. The Gandak River, shared by Nepal and India, is both ecologically and socio-economically vital, but no integrated assessment of its water quality has previously been undertaken. Addressing this gap, this study presents the first comprehensive assessment of water quality in the Gandak River along its entire transboundary stretch from Nepal to India. Correlation analysis and average concentrations of 11 physicochemical parameters and 8 heavy metal(loid)s revealed significant contamination in the upstream, at the India-Nepal border, and in the downstream section of the river, primarily influenced by Mn and Pb concentrations. PCA and PMF analyses identified agriculture (64.2%) as the primary contributor to heavy metal(loid)s pollution, followed by industrial sources (16.2%). The WQI indicated that 67% of the river water is classified as poor quality, while the HPI categorized all regions as highly polluted. Health risk assessment showed non-carcinogenic risks (THI) for children above the safety threshold year-round, with carcinogenic risk (TCR) from arsenic surpassing 10⁻⁴ across seasons. These findings indicate that children are more susceptible to potential health risks from As than adults. This study establishes a critical baseline for heavy metal(loid)s pollution in the Gandak River and highlights the urgency of coordinated monitoring and transboundary management to protect vulnerable communities and safeguard riverine ecosystems under increasing environmental pressure.</p>