Although drought is recognized as one of the major hydroclimatic hazards affecting the Mediterranean Basin, local-scale assessments to support planning for its agricultural, hydrological, and food security impacts remain limited. This study investigates historical and future drought dynamics in Manisa (Western Türkiye) using a multi-scale framework integrating the Standardized Precipitation Index (SPI) and the Standardized Precipitation Evapotranspiration Index (SPEI) with CMIP6 climate projections. A comprehensive dataset including ERA5-Land, CHIRPS, TerraClimate, and station observations was evaluated, revealing strong agreement in temperature but higher uncertainty in precipitation. SPI results indicate recurrent short-term droughts with extreme events reaching −2.5 in 2007–2008, alongside intensified long-term hydrological droughts since the early 1990s, while SPEI reveals a stronger temperature-driven drought signal, peaking near −2.0 during 2020–2024 as the most severe cumulative drought period in the past 40 years. Rapid wet–dry transitions have increased since 2000, indicating a more unstable hydroclimatic regime. Future projections (2025–2100) under a high-emission scenario suggest a progressive intensification of thermally driven drought conditions, with SPEI trends declining more steeply than SPI, indicating that evapotranspiration-driven water deficits may increasingly outweigh precipitation deficits as a driver of future drought risk. These findings offer localized, data-driven evidence relevant to climate adaptation and water resource planning in semi-arid Mediterranean agricultural regions.