Surface water quality is among the significant challenges in the Sutlej River basin, passing through Pakistan's most densely populated province. Currently, the overall surface water quality is grossly polluted, mainly due to the direct discharge of wastewater from the urban areas to the Sutlej River directly or through stream networks. Escherichia coli concentrations vary under extreme weather events like floods and droughts and socioeconomic circumstances like urbanization, population growth, and treatment options. This paper assesses the future E. coli load and concentrations using the Soil and Water Assessment Tool (SWAT) along with scenarios based on Shared Socioeconomic Pathways (SSPs) and Representative Concentration Pathways (RCPs) developed by the Intergovernmental Panel on Climate Change (IPCC). E. coli concentrations according to a more polluted scenario disclose a near and mid future increase by 108% and 173%, and far future increases up to 251% compared to the reference period (baseline) concentrations. The E. coli concentration is reduced by - 54%, - 68%, and - 81% for all the projected time steps compared to the baseline concentrations. While highly improved sewerage and manure management options are adapted, the concentration is further reduced by - 96%, - 101%, and - 105%, respectively, compared to the baseline. Our modeling and scenario matrix study shows that reducing microbiological concentrations in the surface water is possible. Still, it requires rigorous sanitation and treatment options, and socioeconomic variables play an essential role besides climate change to determine the microbiological concentration of water resources and be included in future studies whenever water quality and health risks are considered.