The last two decades of cancer research have seen two major advancements in our ability to treat cancer: precision medicine and immunotherapy. While these approaches have shown striking anticancer efficacy in numerous malignancies, they have not shown similar success and applicability in advanced prostate cancer patients. The fields of precision medicine and immunotherapy have come to realize that targeted therapies are capable of not only inhibiting tumor cell growth, but also promoting antitumor immunity by modulating the tumor microenvironment. Here we examine how personalized medicine can be used to target the tumor immune microenvironment in prostate cancer, with the goal of enhancing clinical responses to immunotherapy.