Efficient anti-tumoral responses can be increased by using combinatorial vaccine strategies. We recently showed that vaccination can be optimized by administering locally diverse molecular or bacterial agents to target and augment anti-tumoral CD8 T-cells in the genital mucosa (GM) and increase regression of cervical cancer in an animal model. Non-muscle invasive bladder cancer is another situation that is easily amenable to local therapies. In contrast to the data obtained in the GM, here we show that intravesical (IVES) instillation of synthetic toll-like receptor (TLR) agonists only modestly induced recruitment of CD8 T-cells in the bladder. However, IVES administration of Ty21a, a live bacterial vaccine against typhoid fever, was much more effective and increased ca. 10-fold the number of total and vaccine-specific CD8 T-cells in the bladder. Comparison of chemokines induced by either CpG (a TLR-9 agonist) or Ty21a in bladder highlighted the preferential increase by the latter of Complement component 5a, CXCL5, CXCL2, CCL8 and CCL5 suggesting their involvement in T-cell attraction to the bladder. IVES Ty21a following vaccination also significantly increased tumor regression as compared to vaccination alone, resulting in 90% of mice survival in an orthotopic murine model of bladder cancer expressing a prototype tumor antigen. Our data demonstrate that combining vaccination with local immunostimulation may be an effective treatment strategy for different types of cancer and also highlight the great potential of the worldwide routinely and safely used Ty21a vaccine in such combinatorial therapies.