This study hypothesized the existence of cultivar-associated correlations between grape berry metabolites and its microbial residents, in Douro wine region. Integrated metabolomics with metabarcoding showed that the microbial biodiversity is not associated to berry sugar concentration, but closely connected to the profile of amino acids, flavonoids and wax compounds, which drove cultivar differentiation together with the prevalence of pathogenic fungi, yeasts and bacteria, mainly Dothideomycetes and Gammaproteobacteria. Over 7000 metabolite-microbiota correlations with ρ >|0.99| exposed a core of 15 metabolites linked to 11 microbial taxa. Serine, oxalate, cyanidin-3-O-glucoside, petunidin-3-O-glucoside, gallic acid, germanicol, sitosterol and erythrodiol correlated negatively to the abundance of most taxa, including Alternaria, Aureobasidium, Pseudopithomyces, Pseudomonas and Sphingomonas. In contrast, phenylalanine, asparagine, alanine, (epi)gallocatechin and procyanidin gallate mediated positive metabolite-OTU correlations. E. necator and A. carbonarius correlated negatively with stigmasterol and amyrin. Complex fungi-bacteria relationships ruled by Dothideomycetes and Alphaproteobacteria further suggest tight host-microbe interactions at the carposphere.