Vertical mixing is fundamental to thermohaline circulation, deep-water ventilation, and biogeochemical cycling in enclosed seas, yet its spatiotemporal variability remains poorly quantified. Using a validated 9-year (2010–2018) 3D ocean circulation model, we identify three distinct vertical mixing hotspots with unique physical drivers: (1) Deep Basin winter convection (December–March, Kh ≈ 0.01 m²/s), driven by surface cooling; (2) Eastern Slope upwelling/frontal hotspot (June–September, Kh ≈ 0.01 m²/s), where shear instability and internal wave breaking overcome strong stratification (N² ≈ 0.0005 s⁻²); and (3) Volga Shelf river plume hotspot (April–August, Kh ≈ 0.01–0.001 m²/s), driven by plume instabilities and bottom friction. From 2015 to 2018, winter mixed-layer depth decreased by 30–50 m and surface Kh declined by a factor of 2–3, consistent with recent interannual variability and strengthened stratification in the region. In contrast, deep Kh (100–200 m) showed a slight increase (typically 0.001 to 0.01 m²/s), indicating vertical decoupling. Nutrient flux estimates show the Eastern Slope sustains summer supply on the order of 10 to 100 μmol N m⁻² day⁻¹ (one to two orders of magnitude higher than the stratified interior ≈ 0.1 μmol N m⁻² day⁻¹), explaining persistent coastal productivity. Deep-water ventilation timescales exceed 2000 years below 300 m, highlighting extreme vulnerability to hypoxia in the isolated deep layers. As basin-scale winter convection weakens under warming, lateral-vertical exchange via slope mixing hotspots becomes increasingly critical. These findings provide a mechanistic framework for physical-biological coupling in enclosed basins and inform fisheries management and climate adaptation in the Caspian Sea and similar systems worldwide.