This is a study using pembrolizumab for first-line treatment of participants with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy. The primary study hypothesis is that pembrolizumab treatment will result in a clinical meaningfully overall response rate (ORR) in participants whose tumors rely on programmed cell death ligand 1 (PD-L1) protein.