Engineered nanomaterials are being developed for a variety of applications. However, the increasing use of nanomaterials has led to concerns about their potential adverse effects on human health and the environment. It is now understood that effective risk assessment of nanomaterials would benefit from a comprehensive understanding of their toxicological mechanisms, which is difficult to achieve with traditional, low-throughput, single-endpoint approaches. However, global omics approaches with which to assess changes in genes, proteins, and metabolites in cells and tissues are now being introduced in nano(eco)toxicology. In a systems toxicology paradigm, quantitative and predictive models of nanomaterial behaviour in a biological system are developed, to support and inform risk assessment. In this chapter, we discuss omics technologies and their application in nanotoxicology.