Vineyards are facing an increase in annual heat waves due to climate change which can interfere with grapevine diseases, and thus with wine quality and/or production. In addition, common practices, notably leaf removal, expose bunches to higher temperatures, particularly during fruit ripening. Such temperature rises modify berry metabolism and potentially the susceptibility to grapevine fungal diseases, such as gray mold caused by Botrytis cinerea (Bc). This fungus, by infecting berries in post-veraison stages, can reduce severely both yield and wine quality. Our research on fruiting cuttings endeavors to elucidate the intricate interplay between heat stress (HS; + 10°C) and tolerance to subsequent Bc infection. To reproduce vineyard microclimate, HS was applied focusing onto the bunch only, at herbaceous stage in Cabernet Sauvignon (CS) and Merlot (M). In vitro test, on detached berries inoculated 22 days post-HS, revealed an enhanced tolerance for CS berries stressed. However M berries, more tolerant than CS ones, were not affected significantly by HS. These results highlight a clear berry response to infection depending on both genetic background and the HS exposure. Based on the major result that fruit ripening (mid-veraison onset, sugar accumulation) and physiology (berry weight and volume) were unaltered significantly following HS, we investigated further the accumulation of preformed defense compounds and fruit physical barriers. We performed berry cuticle composition analyses (i.e. waxes and cutins), skin antifungal tannins assessment and entire-berry metabolomics, assuming that the compounds quantified could potentially account for the heat-induced tolerance. Although a clear difference in metabolites content between CS and M, we highlighted within CS the potential key role of both cutin monomers and skin condensed tannins in the heat-induced tolerance against Bc. Moreover, untargeted metabolomics revealed a range of unfamiliar compounds whose accumulation were potentially contributing to an increased resistance to the pathogen.Read less <