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Variability in individual capacity for hepatic elimination of therapeutic drugs is well recognized and is associated with variable expression and activity of liver enzymes and transporters. Although genotyping offers some degree of stratification, there is often large variability within the same genotype. Direct measurement of protein expression is impractical due to limited access to tissue biopsies. Hence, determination of variability in hepatic drug metabolism and disposition using liquid biopsy (blood samples) is an attractive proposition during drug development and in clinical practice. This study used a multi‐“omic” strategy to establish a liquid biopsy technology intended to assess hepatic capacity for metabolism and disposition in individual patients. Plasma exosomal analysis (n = 29) revealed expression of 533 pharmacologically relevant genes at the RNA level, with 147 genes showing evidence of expression at the …