The application of nanotechnology in phytoremediation of heavy-metal-polluted soil has revitalized this traditional remediation technology with higher efficiencies. Among various material types, micronutrient-based nanomaterials have recently come into the public spotlight because of their positive effects on plant performances without significant perturbation to the environmental media, while their effects and the related mechanisms to enhance the phytoremediation efficiencies remain largely uncovered. In this study, molybdenum trioxide nanoparticles (MoO 3 NPs) and molybdate (Mo 6+ ) were applied in combined heavy-metal-contaminated soils to explore their effects on plant tolerance and phytoextraction ability of a typical Cd hyperaccumulator, Solanum nigrum L. Experimental results indicated that low-level Mo (4 mg kg −1 ) application, especially for MoO 3 NPs, significantly improved the plant performance and Cd accumulation of S. nigrum by activating nutrient assimilation and antioxidative levels, while excessive Mo addition (20 and 40 mg kg −1 ) further exacerbated detrimental effects on plants under combined heavy-metal pressure. Furthermore, nontargeted metabolomic analysis was adopted to uncover the regulating mechanisms of Mo materials on plant responses. Under 4 mg kg −1 treatment, MoO 3 NPs stimulated metabolite expression related to carbohydrate biosynthesis and antioxidative systems to enhance plant tolerance and phytoextraction ability, revealing less metabolic perturbation compared to Mo 6+ treatment. Abscisic acid signaling was considered to be a key regulator contributing to differential regulating pathways between low-level Mo 6+ and MoO 3 NPs treatments. However, under higher Mo levels, both materials led to similar dysregulations in several important pathways concerning amino acid, lipid, and carbohydrate metabolisms. This study provided a theoretical basis for utilizing essential micronutrient-based nanomaterials to facilitate phytoremediation by hyperaccumulators during in situ remediation of heavy metals.