The fast adoption of nanotechnology in agriculture leads to beneficial applications but also generates new problems regarding nanotoxicity in plants. A detailed analysis of engineered nanomaterial (ENM) and plant system interaction is discussed using systems biology as an advanced discovery method throughout this chapter. Plants exhibit both toxic and beneficial consequences from interactions with nanomaterials, which depend on the exposure methods, material composition, and concentration levels. Research using multi-omics methods that combine genomics with transcriptomics, together with proteomics and metabolomics, allows scientists to detect molecular pathways altered by nanoparticle exposures. The combined application of these approaches helps scientists understand how nanoparticles cause oxidative stress while affecting the cells genetically and disrupting signalling and metabolism in plants. Computational modelling and network analysis tools help scientists understand how nanoparticles enter living systems and spread throughout the body and establish predictive methods to evaluate the dangers nanoparticles pose to living beings. The chapter presents protective approaches for nanoparticle risks through designed risk-free nanomaterials alongside bioremediation solutions and discusses why regulatory structures serve as crucial guides for agricultural nanotechnology use. The research demonstrates the requirement for holistic strategies to guarantee sustainable and responsible nanomaterial use in plant science.