Study region: Ganh Hao River, Ca Mau Peninsular, Vietnamese Mekong Delta. Study focus: The study was conducted to determine the extent of pollution by physicochemical parameters and heavy metals through seasonally sampling of the river. The water quality was compared with international and Vietnamese standards, while sediment quality was compared with the Vietnamese standard and pollution indices (Geo- accumulation Index, Contamination Factor, and Pollution Load Index). The principal component analysis (PCA) was employed for explaining the main factors responsible for observed levels of water pollution. The oscillations due to tidal cycles and seasonality were also evaluated by statistical comparison. Based on the logistic regression models, the temporal variability of selected water quality parameters was visualized using QGIS. New hydrological insights: The results showed that the concentrations of nutrients and organic compounds exceeded the allowable standards for surface water quality. The concentrations of heavy metals were below the allowable standard for sediment quality and consistent with the background levels. The influences of the tidal regime and seasonality caused significant changes in water quality. Aquaculture practices and tidal regimes accounted for 79.84% of the total variance in water quality characteristics. The extensive and improved-extensive shrimp culture activities were identified in relation to the variation in water quality, and water quality maps highlighted pollution hotspots. The research results could be useful not only to policymakers in developing water resources management strategies but also likely widespread implications for other rivers beyond the geographical regions.