There has long been debate about how nanoproducts meet agricultural requirements. This study aimed to investigate tomato responses to the long-time foliar application of zinc oxide nanoparticles (ZnO-NP; 0 and 3 mgl.sup.-1) or bulk type (BZnO). Both ZnO-NP and BZnO treatments, especially the nanoform, were significantly capable of improving growth, biomass, and yield. The ZnO-NP treatment upregulated the expression of the R2R3MYB transcription factor by 2.6 folds. The BZnO and ZnO-NP treatments transcriptionally up-regulated WRKY1 gene by 2.5 and 6.4 folds, respectively. The bHLH gene was also upregulated in response to BZnO (2.3-fold) or ZnO-NP (4.7-fold). Moreover, the ZnO-NP application made a contribution to upregulation in the EREB gene whereas the bulk compound did not make a significant change. Upregulation in the HsfA1a gene also resulted from the ZnO-NP (2.8-fold) or BZnO (1.6-fold) supplementation. The MKK2 and CAT genes displayed a similar upregulation trend in response to the supplements by an average of 3-folds. While the application of ZnO-NP slightly down-regulated the histone deacetylases (HDA3) gene by 1.9-fold, indicating epigenetic modification. The supplements, especially the nano-product, enhanced concentrations of K, Fe, and Zn in both leaves and fruits. The concentrations of Chla, Chlb, and carotenoids were increased in response to the BZnO or ZnO-NP treatments. Likewise, BZnO or ZnO-NP mediated an increase in activity of nitrate reductase and proline content in leaves. These treatments increased soluble phenols and phenylalanine ammonia-lyase activity. With a similar trend, the BZnO or ZnO-NP application improved the activities of catalase and peroxidase enzymes. The reinforcement in metaxylem and secondary tissues resulted from the applied supplements. This study provides comprehensive comparative evidence on how ZnO-NPs may remodel the chromatin ultrastructure and transcription program, and confer stress tolerance in crops. This study also underlines the necessity of providing integrated transcriptome and proteome data in future studies.