A holistic framework was introduced to project the potential hydro-meteorological droughts of the Kelantan River basin, Malaysia. The framework integrates the multi-model high-resolution climate projections of the Coordinated Regional Climate Downscaling Experiment – Southeast Asia (CORDEX-SEA) and the widely applied Soil and Water Assessment Tool (SWAT) model. The quantile mapping approach was used to reduce the biases in the CORDEX-SEA projections before applying into SWAT. The SWAT-simulated standardized streamflow index (SSI) was validated with observed data to check the capability of SWAT in drought estimation. The result indicated that SWAT was able to reproduce the historical 1982, 1987 and 1997–1998 droughts and simulate SSI from one to twelve-month scales well, with the NSE and R2 values of 0.74–0.79 and 0.76–0.80, respectively. Overall, the annual precipitation, maximum and minimum temperatures are projected to change from −8.19 to 13.11% (−13.35 to 10.10%), 0.45 to 2.41 °C (0.43 to 3.99 °C) and 0.73 to 2.98 °C (0.70 to 4.69 °C), respectively, by the end of the 21st century under the RCP4.5 (RCP8.5) scenario. This would cause the future annual streamflow to vary from −10.37 to 31.09% and − 19.87 to 13.24% under RCP4.5 and RCP8.5, respectively, with the reductions are mainly found in the north-western region of the basin. Monthly precipitation and streamflow would be likely to decrease in January and February and increase in September. Robust evidence shows that the meteorological drought duration is likely to become longer in the 2081–2100 period under RCP4.5. Meanwhile, there is not enough evidence to claim that hydrological drought will become more significant in the near future.