A 53-year-old man with metastatic bladder cancer was treated with multiple chemotherapy regimens with clear disease progression. At presentation in our clinics, he was symptomatic with severe pain, weight loss, fatigue, pain, and lower extremity edema. Hospice care had been recommended; however, the patient wanted to continue treatment. The patient was started on a novel bladder chemotherapy regimen using a combination of mitoxantrone and paclitaxel. This regimen has been shown to be effective in platinum refractory ovarian cancer but there are no prior data in bladder cancer. The patient's bladder cancer responded dramatically from a clinical, biochemical, and radiographic perspective.