Rapidly warming climate affects water availability for boreal conifer species, thus urging the need for assessing their adaptive capacity to better predict forest vulnerability and resilience under drier climates. In this study, we first used a dendroecological approach to determine the level of climate sensitivity of white spruce (Picea glauca [Moench] Voss) trees grown in a provenance-family common garden. We detected a clear signal of local genetic adaptation to drought, with provenances originating from drier locations showing a higher resilience than those from wetter locations. Based on those results, we further dissected the genomic features underlying white spruce adaptation to drought, by combining gene-environment associations (GEA), genotype-phenotype associations (GPA) and transcriptomics. We identified a set of 285 genes significantly associated with climatic factors or phenotypic traits, among which 110 genes were differentially expressed under drought stress in greenhouse-controlled conditions. The interlinked phenotype-genotype-environment network revealed eight high-confidence genes involved in white spruce adaptation to drought, among which four were also drought-responsive in the expression analysis. Our findings represent a significant step towards the characterization of the genomic basis of drought resilience in conifers, and provide a new opportunity to improve drought resistance of seedlings used in reforestation.