The ability of grapevine cultivars and rootstocks to cope with and adapt to recurring water constraints is the focus of this study. The contribution of intrinsic (epigenetic) and extrinsic (rootzone microbial community) factors to water stress resilience will be discussed. The study was conducted in a validated model vineyard where three scion cultivars (Pinotage, Shiraz, and Cabernet Sauvignon) on two rootstocks (Richter 110 and USVIT8-7) grow under recurring seasonal water constraint (and control) scenarios since planting (in 2020). Comprehensive profiling of the site, soil, atmospheric conditions, plants, and their physiological responses provide contextual data for the analyses conducted.