Metabolomics serves as a crucial instrument for scientists employing advanced post-genomics methodologies to uncover metabolite networks and their interrelationships. It pertains to the examination of the metabolome, which refers to the array of small molecules synthesized by cells that govern the metabolic functions of an organism. This concept has emerged and progressed significantly over the past decade. It encompasses the thorough analysis of metabolites within a biological specimen, or the systematic identification and quantification of all metabolites present within a specific organism or biological sample. As direct indicators of metabolic processes, metabolomics aligns more closely with phenotypic expressions when compared to genomics, transcriptomics, and proteomics. Researchers can explore the metabolome through both targeted and untargeted methodologies. Untargeted metabolomics, often referred to as “global metabolomics,” employs an unbiased screening approach to detect thousands of metabolites in a single analytical run, facilitating exploratory investigations of unidentified metabolites. In contrast, targeted metabolomics concentrates on quantifying a specific set of metabolites relevant to the pathway of interest. The domain of small molecule biochemistry in plant research has advanced significantly, attributed to the enhanced resolution afforded by techniques such as nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), along with LC-MS, GC-MS, and robust chemometric analytical software. These methodologies enable the concurrent analysis and comparison of thousands of compounds. Nanomaterials are attracting global interest due to their ability to protect plant growth from environmental stressors, including drought, salinity, heavy metal toxicity, extreme temperatures, and flooding. In light of current and forecasted challenges in sustainable agricultural production, nanoparticles (NPs) are viewed as viable and efficient approaches to improving crop yields by increasing a plant’s resilience to abiotic stress conditions. Nanomaterials have been connected to plant biochemical, physiological, and molecular responses to drought stress, and they have been used as a strategy to boost plant temperature resilience. This chapter covers and updates the use of metabolomic technologies to investigate the physio-biochemical reactions of stressed plants.