Disparities in cancer are common among the racial and ethnical minorities in the United States and are of significant social and clinical concern. Prostate cancer is the most commonly diagnosed non-cutaneous malignancy in American men and exhibits substantial racial disparities with African American men bearing the highest burden in terms of incidence and mortality. A multitude of factors, including socioeconomic, behavioral, and access to healthcare, have been implicated as the underlying causes of such disparities. More recent data also suggest that there are inherent genetic and biological differences in prostate tumors of patients having distinct racial backgrounds. Tumor microenvironment has tremendous impact on the course of cancer progression and clinical outcome and may also contribute to the racial disparities observed in prostate cancer. A better understanding of critical differences in the tumor microenvironment components will provide newer directions to study the biological causes of prostate cancer health disparities and may identify novel therapeutic targets. This review discusses the findings related to the tumor microenvironment differences between the of African American and Caucasian American prostate cancer patients to suggest their potential significance in prostate cancer disparities.