Background/Objectives: Immunotherapy is an essential part of metastatic bladder cancer treatment. Our main objective was to study the prognostic value of FDG-PET/CT in early assessment of response to Pembrolizumab in metastatic bladder cancers using PERCIST5, imPERCIST5, and PERCIMT criteria. Methods: A total of 42 patients were evaluated with FDG-PET/CT at baseline and after 3–4 cycles of Pembrolizumab. Treatment response was blindly assessed with PERCIST5, imPERCIST5, and PERCIMT. Imaging and clinical data were collected. Progression was defined clinically using oncologist reports. Results: A total of 37 patients were evaluable with the PERCIST5 and imPERCIST5 criteria and included in the analysis. Median disease-specific progression-free survival (PFS) and overall survival (OS) were 152 and 363 days, respectively. All response criteria were significantly associated with PFS. When response was dichotomized in responders versus non-responders all scores were significantly associated with OS. When response was dichotomized in progressors versus non-progressors, only PERCIST5 (hazard ratio (HR) 2.2) and PERCIMT (HR 2.6) were significantly associated with OS, while imPERCIST was not (HR 1.6). Two patients had pseudoprogression (5%), both being adequately classified as non-progressors with PERCIMT criteria. Conclusions: Early response to immunotherapy as assessed with FDG-PET is a strong prognostic factor in bladder cancer patients, especially using the PERCIST5 or PERCIMT criteria. The latter seems clinically useful as it is simple to perform and its specific definition of metabolic progression correctly ruled-out patients with significant clinical benefit of Pembrolizumab in our study.