Individual differences in drug response have always existed in clinical treatment. Many non-genetic factors show non-negligible impacts on personalized medicine. Emerging studies have demonstrated epigenetic could connect non-genetic factors and individual difference in treatment. We used systematic retrieval methods and reviewed studies that showed individual factors’ impact on DNA methylation of ADME genes. In total, 63 studies were included, and half(n=32) were cohort studies. Six aspects of individual factors were summarized from the perspective of personalized medicine: parental exposure, environmental pollutants exposure, obesity and diet, drugs, gender and others. The largest number of studies (n=11) studied methylation of ABCG1. Most studies showed these non-genetic factors could result in a significant DNA methylation alteration in ADME genes, which subsequently affect the process of drug metabolism. However, the underlying mechanisms remain unknown. Finally, we put forward some views for future research.