Non-urothelial histologic variants of bladder cancer (non-UC), including adenocarcinoma, squamous cell carcinoma (SCC), and neuroendocrine (NE) tumors, are rare, aggressive cancers. The genomic landscape of these tumors is heterogeneous, making a tailored therapy approach challenging. It is unclear if combined ICB of PD-L1 and CTLA-4 pathways will be effective in non-UC variants.