In recent years, the relationship between plants and nanoparticles (NPs) has been the subject of extensive research interest. Hence, an ever-increasing number of perspectives connected with both the positive and adverse consequences of NPs application in plants are highlighted in this review. On the other hand, nanoparticles and their interactive effects on plants have raised concern regarding their harmful aspects. There are complex mechanisms evolved in plants for controlling the uptake, accumulation, and mobilization of nanoparticles that need to be discussed further, especially in the context of proteomics and genetic level. To fill this gap, there is a dire need for the integration and application of multiomics in plants to identify sensitive biomarkers responding to engineered NPs and to provide mechanistic insights in order to design safer and enhanced nano-enabled products for agriculture. For this purpose, transcriptomic technologies have essentially contributed to understanding of the molecular systems in plants against nanoparticle stress by laying out an association between gene expression and cell response. In light of this background, the current article attempts to summarize a variety of recent transcriptomic and proteomic contributions that have been made to establishing the genetic basis of nanoparticle uptake and the mechanism of stress response. The present article also looks at recent proteomic and transcriptomic studies to learn more about the intricate regulatory network that connects plant and nanoparticle stress responses.