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 treatment differences. We used systematic retrieval methods and reviewed studies that showed individual factors' impact on DNA methylation of drug metabolism genes. In total, 68 studies were included, and half(n = 36) 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 most research (n = 11) focused on ABCG1 methylation. The majority of studies showed non‐genetic factors could result in a significant DNA methylation alteration in drug metabolism genes, which subsequently affects the pharmacokinetic processes. However, the underlying mechanism remained unknown. Finally, some viewpoints were presented for future research.This article is protected by copyright. All rights reserved.