Purpose: In NABUCCO, the safety and efficacy of preoperative ipilimumab plus nivolumab were assessed in stage III urothelial cancer. Encouraging responses were achieved, and ipilimumab 3 mg/kg (ipilimumab-high) seemed more effective than ipilimumab 1 mg/kg (ipilimumab-low). We explored ipilimumab plus nivolumab response biomarkers and tumor microenvironment (TME) treatment dynamics. Patients and Methods: Baseline formalin-fixed, paraffinembedded tumor tissue was analyzed using PD-L1 IHC (n ¼ 51) and whole-exome and transcriptome sequencing (both n ¼ 53) and correlated with response. Baseline infiltration of CD8⁺ T cells (n ¼ 51) and at cystectomy (n ¼ 42) was examined. Single-cell RNA sequencing (scRNA-seq) of CD3⁺ T cells was conducted on on-treatment resection tissue of two responders to ipilimumab-high to explore the characteristics of CD8⁺ T cells within the TME. Results: High tumor mutational burden and PD-L1 positivity were associated with response to ipilimumab plus nivolumab. Nonresponding patients exhibited increased expression of a TGFβ signature. We observed increased transcription of the g2m checkpoint and e2f target in responders to ipilimumab-high and enhanced transcription of IFN-α and IFN-γ hallmarks in responders to ipilimumab-low. CD8⁺TCF7⁺ T cells accumulated in the TME of responders to ipilimumab-high. scRNA-seq of CD8A⁺TCF7⁺ T cells demonstrated enhanced expression of IL7R, CCR7, GPR15, XCL1, SELL, and LEF1. Conclusions: Our data indicate that tumor mutational burden, PD-L1, and TGFβ are potential biomarkers for response to ipilimumab plus nivolumab in stage III urothelial cancer. An inflammatory TME might be relevant for responding to ipilimumab-low. We found that in responders to ipilimumabhigh, TCF7⁺CD8⁺ T cells accumulated in the TME. scRNA-seq in two responders suggested that TCF7⁺CD8A⁺ T cells express genes associated with immunologic memory formation and T-cell homing.