The lower Meghna River, the easternmost part of the Ganges Delta, faces severe anthropogenic perturbations as it receives a huge discharge and industrial effluents. To measure the metal concentrations and human health hazards, edible tissues of 15 commercially important fish species were collected from the local fish markets and the lower Meghna River, Bangladesh. Trace and heavy metals such as Pb, Cr, Cu, Zn, Mn, Fe, Hg, Ni, Ca, Co, Se, Rb, Sr, and As were detected using the Energy Dispersive X-ray Fluorescence (EDXRF) method. The hierarchy of mean metal concentrations obtained was: Fe (162.198 mg/kg) > Zn (113.326 mg/kg) > Ca (87.828 mg/kg) > Sr (75.139 mg/kg) > Cu (36.438 mg/kg) > Se (9.087 mg/kg) > Cr (7.336 mg/kg) > Mn (6.637 mg/kg) > Co (3.474 mg/kg) > Rb (1.912 mg/kg) > Hg (1.657 mg/kg) > Ni (1.467 mg/kg) > Pb (0.521 mg/kg) > As (BDL). Based on the metal concentration obtained, the carnivorous species contained more metals than omnivores and herbivores. Similarly, the euryhaline and benthic feeder fishes had more metals than the stenohalines and demersal fishes. The metal pollution index (MPI) suggested that the highly consumed fish species Tilapia (Oreochromis mossambicus) and Rui (Labeo rohita) accumulated higher metals than other fishes. Both the Targeted Hazard Quotient (THQ) and Hazard Index (HI) values for adult and child consumers were <1, indicating that consumers would not experience the non-carcinogenic health effects. Although children were more susceptible than adults, carcinogenic risk (CR) exposure of Cr for all the consumers was found in the acceptable range (10−6 to 10−4 ), but the CR exposure of Pb was negligible for all the consumers. The correlation, principal component analysis (PCA), and cluster analysis were conducted to identify the sources of metals identified from the fish tissue. The results indicated that the probable sources of the pollutants were anthropogenic, arising from agricultural activities, electroplating materials, and lubricants used near the study area. However, the present study showed a different metal concentration in the samples at different levels but within the threshold levels non-carcinogenic and carcinogenic health risks; hence, the fishes of the area, in general, are safe for human consumption.