Novel tools that evaluate the genetic drivers and transcriptional responses to drug and chemical exposures have the potential to add important insights into toxicology evaluation. In this session, novel tools will be described that demonstrate utility for safety and risk assessment pipelines. These tools span (1) DNA methylation analysis, rodent population models that enable assessment of human population dynamics in susceptibility and avenues for precision medicine, (2) high-throughput transcriptomic screens that enable sensitive measures of chemical potency, (3) gene expression network analysis that informs intracellular chemical effects, and (4) yeast genetic screens that identify genetic susceptibility factors and inform toxicity mode of action.