Microbial-based approaches have been proposed as a solution to decrease the use of chemical fertilizers in agriculture. Among these, the most promising candidates are arbuscular mycorrhizal fungi (AMF), with their ability to extend the root surface and absorb phosphate, and phosphate solubilizing bacteria (PSB), but their effectiveness has been shown to depend on plant genetic diversity. With the aim of identifying genetic markers explaining plant differential responses to soil-beneficial microbes, we monitored a panel of 128 fully sequenced varieties of Lactuca sativa in a controlled condition of P starvation, treated with AMF and PSB. Results showed a strong effect of the lettuce genetic variation on the plant physiological and morphological response to the inoculum. Through genome-wide association studies (GWAS), we identified specific genetic regions associated with variations in leaf phosphate and shoot biomass in response to the treatment. Beyond genetic factors, root-associated microbes played a crucial role in shaping key plant nutritional parameters, with a change in fungal {beta}-diversity and an increase in bacterial -diversity associated with progressively higher leaf phosphate and shoot biomass response. In conclusion, we highlighted key genetic and physiological mechanisms that could play a crucial role in enhancing microbial treatments for optimizing plant phosphate management.