Rapid unplanned industrialization and urbanization in Bangladesh have led to significant pollution and degradation of freshwater sources, highlighting the need for preservation as a fundamental human right. Untreated wastewater discharged from industries contributes to heavy metal toxicity, posing a significant risk to aquatic organisms, wildlife, and human health. The Meghna River, a potential source of freshwater for the capital city, Dhaka, and the sustainer of diverse aquatic ecosystems and habitats, also serves as a sink for untreated industrial effluents containing heavy metal contaminants. Hence, to mitigate heavy metal contamination and preserve the ecosystem and human health, it is crucial to regularly monitor the water quality and heavy metal concentration of the river. However, using conventional techniques to evaluate heavy metal pollution in large areas like rivers comes with challenges, including inaccessibility, time, and cost. With the advent of advanced remote sensing technologies, using Satellite Earth Observation Data (EO) and correlating high-resolution satellite images and in-situ data offers the potential to assess the pollution level of the study area effectively. In this study, sentinel-2 satellite images were utilized to assess the heavy metal concentration of the Meghna River. Samples were collected during the Monsoon and Post Monsoon period within the proximity of industrial areas near Meghna Bridge, Narayanganj. The laboratory analysis of heavy metal concentration was conducted using the ICP mass spectrometer. Multiple linear regression (MLR) models were established between measured heavy metal concentrations and spectral reflectances of different bands or band ratios at the corresponding sampling points. The equations generated using the MLR were further applied to the satellite images for zoning the concentration level of heavy metal in the study area. The accuracy of the developed models was examined by Pearson correlation coefficients, and the estimated values generated from the model were further compared with the observed values. The results indicated a significant correlation for Hg, Co, Zn, and As with the spectral reflectance data.