Cancer is a leading cause of mortality and is intensively treated with chemotherapy, surgery, and radiation. Precision oncology in the form of personalized cancer medicines developed as result of advances in the Human Genome Project (HGP), new understandings of the role that the immune system plays in cancer, and novel technologies such as liquid biopsy that allow for tumor monitoring and characterizing tumor heterogeneity. Through the Cancer Genome Atlas, clinically actionable genetic alterations were discovered for effective targeted therapies. The cancer-immunity cycle proposed steps for how the immune system targets tumors and was crucial in the development of cancer immunotherapies. A bispecific antibody for acute lymphoblastic leukemia, antibody drug conjugates for cervical cancer, and chimeric antigen T cell therapy for multiple myeloma are described as examples of personalized cancer medicines. Personalized medicine in cancer has led to a paradigm shift in oncology, leading to new understandings of cancer.