The field of metabolomics continues to grow rapidly over the last decade and has proven to be a powerful technique in predicting and explaining complex phenotypes in various biological systems. As one of the ‘omic’ technology, metabolomics has exciting applications in varied fields including medical science, synthetic biology, medicine and predictive modelling of plant, animal and microbial systems. Integrated application with genomics, transcriptomics and proteomics provide greater understanding of global system biology. Metabolomics is often considered a powerful tool to provide an instantaneous snapshot of the physiology of a cell. It is increasingly being used to characterize the interaction of organism with their environment. Although thermal conditions influence the development of living organism in a wide variety of ways, this topic has been recently ignored in humans. This review reintroduces thermal conditions as a topic of importance by presenting an example of how thermal conditions influence various metabolic pathways. The first section highlights the advances in metabolomics technologies followed by the effects and recent studies of organism function and metabolic responses to thermal stress, including investigations of heat and cold stress are reviewed. This review forms the basis for future studies to detect early biomarkers for thermal stress in humans and identifying population at risk. Furthermore, it can be used to develop methods to provide protection to the body against environmental insult, thereby, reducing the adverse response to thermal stress.