Microplastics (MPs) and nanoplastics (NPs) have inevitably entered and accumulated in terrestrial ecosystems. Recently, the report on MPs/NPs taken-up by crop plants has raised particular concerns. However, molecular mechanisms underlying the interaction of MPs/NPs and crop plant are still vague and elusive. To address this scientific gap, we identified differentially expressed genes (DEGs) and performed co-expression network analyses in hydroponically grown wheat (Triticum aestivum L.) with ambient polystyrene NPs (PSNPs) concentration (0-10 mg/L). PSNPs could significantly shape the gene expression pattern in wheat with a tissue-specific mode. Four regulatory modules associated with the plant performance and nutrient capture were identified using WGCNA analysis. In addition, carbon metabolism, amino acid biosynthesis, MAPK signaling pathway-plant, plant hormone signal transduction, and plant-pathogen interaction were the most enriched KEGG pathways for all DEGs and target module eigengenes. These results confirm that NPs-induced genetic changes are the dominating driven forces for the observed plant growth or defense responses, shedding new light on the molecular mechanism and environmental implication behind the interaction of NPs and crop plants.