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Abstract Vanadium (V) pollution potentially threatens human health. Here, it is found thatnsp1andnsp2,Rhizobiumsymbiosis defective mutants ofMedicago truncatula, are sensitive to V. Concentrations of phosphorus (P), iron (Fe), and sulfur (S) with V are negatively correlated in the shoots of wild‐type R108, but not in mutantnsp1andnsp2shoots. Mutations in the P transporterPHT1,PHO1, andVPTfamilies, Fe transporterIRT1, and S transporterSULTR1/3/4family confer varying degrees of V tolerance on plants. Among these gene families,MtPT1,MtZIP6,MtZIP9, andMtSULTR1; 1in R108 roots are significantly inhibited by V stress, whileMtPHO1; 2,MtVPT2, andMtVPT3are significantly induced. Overexpression ofArabidopsis thaliana VPT1orM. truncatula MtVPT3increases plant V tolerance. However, the response of these genes to V is weakened innsp1ornsp2and influenced by soil microorganisms. Mutations inNSPsreduce rhizobacterial diversity under V stress and simplify the V‐responsive operational taxonomic unit modules in co‐occurrence networks. Furthermore, R108 recruits more beneficial rhizobacteria related to V, P, Fe, and S than doesnsp1ornsp2. Thus, NSPs can modulate the accumulation and tolerance of legumes to V through P, Fe, and S transporters, ion homeostasis, and rhizobacterial community responses.