Developing drought-tolerant crops is an important strategy to mitigate climate change impacts. Modulating root system function provides opportunities to improve crop yield under biotic and abiotic stresses. With this aim, a commercial hybrid tomato variety was grafted on a geno-typed population of 123 recombinant inbred lines (RILs) derived from Solanum pimpinellifolium, and compared with self-and non-grafted controls, under contrasting watering treatments (100% vs. 70% of crop evapotranspiration). Drought tolerance was genetically analyzed for vegetative and flower-ing traits, and root xylem sap phytohormone and nutrient composition. Under water deficit, around 25% of RILs conferred larger total shoot dry weight than controls. Reproductive and vegetative traits under water deficit were highly and positively correlated to the shoot water content. This association was genetically supported by linkage of quantitative trait loci (QTL) controlling these traits within four genomic regions. From a total of 83 significant QTLs, most were irrigation-regime specific. The gene contents of 8 out of 12 genomic regions containing 46 QTLs were found significantly enriched at certain GO terms and some candidate genes from diverse gene families were identified. Thus, grafting commercial varieties onto selected rootstocks derived from S. pimpinelli-folium provides a viable strategy to enhance drought tolerance in tomato. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.