The presence of chronic and toxic Per-and poly-fluoroalkyl substances (PFAS) and Heavy metal substances in a large aquatic ecosystem shows the possible threats to human and environmental health. This study presents a complete evaluation of the origin and distribution of the contaminants in line with PFAS and heavy metals in the Bakkhali river and Cox's Bazar Coastal waters of Bangladesh. Water samples had been collected from the riverine and coastal environments and analyzed for 23 PFAS compounds and 10 heavy metals. The results exhibited significant spatial variations in the concentrations and compositions of those pollutants with overall PFAS concentrations with various 0.68 to 0.94 μg/L throughout sampling stations. Short chain PFAS which includes PFBA and PFPeA were dominant inside the upstream river samples that is signifying pollution from the industrial discharges and urban runoff. The long-chain PFAS including PFTrDA and Et-FOSE were more concentrated in coastal waters which is suggesting marine-based sources. Heavy metal analysis showed increased levels of As, Cr, Cu at specific sampling stations, pointing to localized pollution from industrial and agricultural activities. Exploratory analysis and compositional patterns suggest that contamination may originate from a combination of industrial discharge, urban runoff, and marine-related sources. These findings are considered indicative rather than conclusive given the limited number of sampling stations (N = 7). The strong positive correlations between various PFAS components (r > 0.8) suggest possible co-occurrence patterns consistent with shared industrial sources; however, these patterns should be interpreted with caution given the limited sample size (N = 7). Water quality assessment using various indices showed concerning pollution levels at about 85.7% of samples exceeded acceptable. Heavy Metal Pollution Index limits, while 71.4% showed serious contamination according to Nemerow Pollution Index and Single Factor Pollution Index. Also, the assessment of ecological risk showed low to moderate environmental impact throughout all stations. The presence of these toxic “forever chemicals” and heavy metals in the Bakkhali River estuarine and adjacent coastal environment may pose localized ecological and human health concerns through long-term environmental persistence and potential bioaccumulation. Those results emphasize the pressing need for non-stop monitoring and regulatory frameworks so that the long-term ecological effects of these pollutants and their bioaccumulation within the food chain can be reduced to assess the threats to the local population.