In the Indus River Basin, various hydrological modeling studies have been conducted in the context of climate change scenarios. However, none of these studies addressed the impact of socio-economic along with the climate change scenarios on sustainable water demand and supply. This study focused on socio-economic and Intergovernmental Panel on Climate Change (IPCC) Representative Concentration Pathways (RCPs) scenarios (RCP4.5 and RCP8.5) for 2015–2050 in the Water Evaluation and Planning (WEAP) model were used for future projection of water availability and demand. The WEAP model calibration and validation statistics of Nash–Sutcliffe efficiency and coefficient of determination values were 0.85, 0.86 and 0.89, 0.87, respectively. As per the reference scenarios results by 2050, water demand would increase 11% for domestic and 55% for agriculture and livestock sectors. The high population growth scenario reveals that by 2050, with an increase in the water consumption from 82.9 m3 per capita per day by the year 2015 to 120 m3 per capita per day, unmet water demands in all sectors will increase to 50%. The IPCC climate change scenario projected the average change in precipitation and temperature would be about 15.22% and 274.07 K to 274.92 K by the end of 2035.