Microplastics and nanoplastics (NPs) are pollutants of global concern. However, the understanding of the combined effects of NPs and other pollutants in the soil-plant system remains limited, particularly for polyethylene (PE), the primary component of agricultural films. This study investigated the effects of PE NPs (0.5 %, w/w), fungicide tebuconazole (Te, 10 mg·kg -1 ), and cadmium (Cd, 4.0 mg·kg -1 ) on the soil-wheat system under single and combined exposures. The synergistic toxicity observed between NPs and Te impacted the nutritional conditions and antioxidant mechanisms of the soil-wheat system. The NPs increased the concentration of Cd in roots and the proportion of bioavailable Cd, exacerbating oxidative stress in wheat and inhibiting biomass. The soil-wheat system responded to stress by upregulating or downregulating pathways related to carbohydrate, amino acid, and sugar metabolism under various treatments. Sixteen functional genes associated with carbohydrate metabolism, amino acid metabolism, energy utilization, and gene repair at KEGG level 3 were employed to sustain microenvironmental homeostasis. Correlation analysis between microorganisms and environmental factors showed that various PGPG played roles in maintaining the health of the soil-wheat system. These results help to elucidate the comprehensive effects of NPs with other pollutants on the soil-plant system and provide new perspectives for toxic mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)