Background: In Egypt, Urinary bladder carcinoma is a common malignancy accounting for 14.3% of total malignancies in both sexes with a 3:1 M: F ratio. To reduce bladder cancer morbidity and mortality, identification of tumor markers specific enough for prognosis and can serve as an effective anti-cancer target is urgent. The purpose of this study is to evaluate the role of Trop2, Cyclin D1, FOXP3 and their relationship with the established clinicopathological parameters and overall survival of bladder cancer patients. Methods: Using the standard immunohistochemical technique in 80 primary bladder carcinomas and 20 specimens as non-neoplastic groups. The malignant group included 50 cases of muscle-invasive and 30 cases of non-muscle invasive bladder cancer. Results: significant association of overexpressed Trop2 and FOXP3 with high grade, advanced stage, lymph node involvement, and high mitotic count. On the other hand, Cyclin D1 displayed a favorable prognostic impact and an inverse relation with Trop2 and FOXP3. A direct correlation between both FOXP3 expression in malignant cells and peritumoral TIL FOXP3+ expression was displayed. Trop2, Cyclin D1, FOXP3 expression didn't affect the overall survival of the studied sample. Conclusions: The inverse relation between Cyclin D1 and Trop2 proposes the consumption of Cyclin D1 by Trop2 as a ligand in the urinary bladder carcinogenesis. A synergistic role and a cross-talk between TIL FOXP3+ and tumoral FOXP3 + cells are anticipated. Trop2 and FOXP3 could be a promising potential biomarkers for identifying patients with poor prognostic factors in bladder cancer serving as potential targets for cancer therapy