Cancer immunotherapy, which aims to eradicate tumor cells with the patient’s own immune system, needs to be individualized the same as other therapeutic strategies, because only a specific group of patients clinically respond to the therapy and nonresponders are at a high risk of severe adverse effects. Therefore, the process of trial and error for selecting the best therapeutic regime imposes side effects and high costs on patients and governments. In current years, personalized medicine has received a great deal of attention. In personalized medicine, evidence obtained from the genomic, proteomic, microbiome, and immune profile, lifestyle, and clinical symptoms from each patient is analyzed for finding the most effective therapy. It is expected that personalized medicine revolutionizes immune-oncology and leads to developing a new generation of immunotherapeutics with high specificity, efficacy, and least side effects. However, the development of personalized medicine faces some challenges that medical health societies and governments should consider. This chapter offers a comprehensive review of different aspects of personalized immune-oncology.