The Lam Phaniang River Basin is one of the areas in Northeast Thailand that experiences persistent drought almost every year. Therefore, this study was focused on the assessment of drought severity and vulnerability in the Lam Phaniang River Basin. The evaluation of drought severity was based on the Drought Hazard Index (DHI), which was derived from the Standardized Precipitation-Evapotranspiration Index (SPEI) calculated for 3-month (short-term), 12-month (intermediate-term), and 24-month (long-term) periods. Drought vulnerability was assessed by the Drought Vulnerability Index (DVI), which relied on water shortage, water demand, and runoff calculated from the WEAP model, and the Gross Provincial Product (GPP) data. A drought risk map was generated by multiplying the DHI and DVI indices, and the drought risk level was then defined afterwards. The CNRM-CM5, EC-EARTH, and NorESM1-M global climate simulations, and the TerrSet software were used to evaluate the potential impacts of future climate under RCPs 4.5 and 8.5, and land use during 2021–2100, respectively. The main findings compared to baseline (2000–2017) revealed that the average results of future rainfall, and maximum and minimum temperatures were expected to increase by 1.41 mm, and 0.015 °C/year and 0.019 °C/year, respectively, under RCP 4.5 and by 2.72 mm, and 0.034 °C/year and 0.044 °C/year, respectively, under RCP 8.5. During 2061–2080 under RCP 8.5, the future annual water demand and water shortage were projected to decrease by a maximum of 31.81% and 51.61%, respectively. Obviously, in the Lam Phaniang River Basin, the upper and lower parts were mainly dominated by low and moderate drought risk levels at all time scales under RCPs 4.5 and 8.5. Focusing on the central part, from 2021–2040, a very high risk of intermediate- and long-term droughts under RCPs 4.5 and 8.5 dominated, and occurred under RCP 8.5 from 2041–2060. From 2061 to 2080, at all time scales, the highest risk was identified under RCP 4.5, while low and moderate levels were found under RCP 8.5. From 2081–2100, the central region was found to be at low and moderate risk at all time scales under RCPs 4.5 and 8.5. Eventually, the obtained findings will enable stakeholders to formulate better proactive drought monitoring, so that preparedness, adaptation, and resilience to droughts can be strengthened.