This study explored morphological, physiological, molecular, and epigenetic responses of tomatoes (Solanum lycopersicum) to soil contamination with polyethylene nanoplastics (PENP; 0.01, 0.1, and 1 gkg-1 soil). The PENP pollution led to severe changes in plant morphogenesis. The PENP treatments were associated with decreased plant biomass, reduced internode length, delayed flowering, and prolonged fruit ripening. Abnormal inflorescences, flowers, and fruits observed in the PENP-exposed seedlings support genetic changes and meristem dysfunction. Exposure of seedlings to PENP increased H2O2 accumulation and damaged membranes, implying oxidative stress. The PENP treatments induced activities of catalase (EC1.11.1.6), peroxidase (EC1.11.1.7), and phenylalanine ammonia-lyase (EC4.3.1.24) enzymes. Soil contamination with PENP also decreased the net photosynthesis, maximum photosystem efficiency, stomatal conductance, and transpiration rate. The nanopollutant upregulated the expression of the histone deacetylase (HDA3) gene and R2R3MYB transcription factor. However, the AP2a gene was down-regulated in response to the PENP treatment. Besides, EPNP epigenetically contributed to changes in DNA methylation. The concentrations of proline, soluble phenols, and flavonoids also displayed an upward trend in response to the applied PENP treatments. The long-term exposure of seedlings to PENP influenced fruit biomass, firmness, ascorbate, lycopene, and flavonoid content. These findings raise concerns about the hazardous aspects of PENP to agricultural ecosystems and food security.