: A high baseline neutrophil-to-lymphocyte ratio (NLR) is a poor prognostic factor in various cancers. However, its predictive role in metastatic bladder cancer (mBC) treated with immunotherapy is unclear. In this study, we aimed to investigate the relationship between the baseline and change in NLR and overall survival in mBC patients treated with immunotherapy, with the potential to significantly impact patient care. : A retrospective analysis was conducted on 56 mBC patients who received second-line immunotherapy after progressing on platinum-based chemotherapy. Patients were classified into high and low NLR groups using a cutoff value of 3.3. A further division was made based on NLR changes after two cycles of immunotherapy: whether NLR increased (≥10%) or decreased (≥10%). The endpoint was to estimate the association between clinicopathological features and survival outcomes. : The study included 56 patients, with a median age of 66.6 years and a male-to-female ratio of 2.3:1. A low baseline NLR was associated with better OS than a high baseline NLR ( = 0.005). After two immunotherapy cycles, patients with a decreased NLR (≥10%) had significantly longer OS than those with an increased NLR (≥10%), regardless of the baseline NLR ( = 0.003). The overall median survival was 15 months, with 10 months for the NLR-increased group and not reached for the NLR-decreased group. : Our study highlights the potential of baseline NLR and early changes in NLR as valuable prognostic markers for mBC patients receiving immunotherapy. Elevated neutrophils and lymphopenia negatively impact prognosis and treatment effectiveness, and NLR shows promise as a prognostic marker, inspiring further research and potential improvements in patient care.