Background: The Human Genome Project has unleashed the power of genomics in clinical practice as a choice of individualized therapy, particularly in cancer treatment. Pharmacogenomics is an interdisciplinary field of genomics that deals with drug response, based on individual genetic makeup. Objective: The main genetic events associated with carcinogenesis activate oncogenes or inactivate tumor-suppressor genes. Therefore, drugs should be specific to inactivate or regulate these mutant genes and their protein products for effective cancer treatment. In this review, we summarize how polymedication decisions in cancer treatments based on the evaluation of cytochrome P450 (CYP450) polymorphisms are applied for pharmaco-genetic assessment of anticancer therapy outcomes. Results: However, multiple genetic events linked, inactivating a single mutant gene prod-uct, may be insufficient to inhibit tumor progress. Thus, genomics and pharmacogenetics directly influence a patient’s response and aid in guiding clinicians to select the safest and most effective combination of medications for a cancer patient from the initial prescrip-tion. Conclusion: This review outlines the roles of oncogenes, the importance of cytochrome P450 (CYP450) in cancer susceptibility, and its impact on drug metabolism, proposing combined approaches to achieve precision therapy. © 2020 Bentham Science Publishers.