Pronounced hydrological seasonality and highly dynamic groundwater systems create complex and spatially heterogeneous hydrogeochemical conditions in arid inland river basins. This complexity hampers reliable source-process identification and complicates effective groundwater management. To address these challenges, an integrated multi-method approach was applied, combining self-organizing map (SOM), positive matrix factorization (PMF), hydrochemical diagrams, isotope tracing, and health risk assessment. In the Hotan Oasis, this approach systematically characterized groundwater hydrochemistry and quantified its controlling mechanisms. Groundwater samples were classified into three clusters (C1, C2, C3), representing different hydrochemical patterns. PMF identified six driving factors (F1-F6) with contributions of 46.90%, 20.79%, 9.10%, 8.86%, 7.36%, and 6.99%, indicating that the groundwater composition was jointly controlled by natural hydrogeochemical processes and anthropogenic inputs. Seasonal differences were pronounced: wet-season recharge enhanced dilution and mineral leaching, whereas dry-season conditions intensified evaporationdriven solute enrichment. Agricultural pollution persisted as a background anthropogenic signal. Health risk assessment indicated fluoride (F-) as the primary non-carcinogenic hazard, especially for infants and children, while localized nitrate enrichment also required attention. This study establishes an integrated source-process-risk framework for groundwater evolution in data-limited, process-complex arid inland river basins. The findings provide mechanistic insights and support adaptive water management in fragile oases and other groundwater-dependent dryland environments.