Introduction: This session will discuss how genetic variants and tissue-specific expression of drug-metabolizing enzymes could affect the activation, pharmacokinetics, and therapeutic efficacy of various prodrugs with a focus on antiviral and anticancer medications. The session will stimulate the discussion regarding how to use genetic variants and tissue-specific proteomics information of drug-metabolizing enzymes to improve the design and delivery of prodrugs and enhance the efficacy and safety of prodrug pharmacotherapy.