Immunotherapy is effective in a small percentage of patients with cancer and no reliable predictive biomarkers are currently available. Artificial Intelligence algorithms may automatically quantify radiologic characteristics associated with disease response to medical treatments. We investigated an innovative approach based on a 3-dimensional (3D) deep radiomics pipeline to classify visual features of chest-abdomen computed tomography (CT) scans with the aim of distinguishing disease control from progressive disease to immune checkpoint inhibitors (ICIs). Forty-two consecutive patients with metastatic urothelial cancer had progressed on first-line platinum-based chemotherapy and had baseline CT scans at immunotherapy initiation. The 3D-pipeline included self-learned visual features and a deep self-attention mechanism. According to the outcome to the ICIs, a 3D deep classifier semiautomatically categorized the most discriminative region of interest on the CT scans. With a median follow-up of 13.3 months (95% CI, 11.1-15.6), the median overall survival was 8.5 months (95% CI, 3.1-13.8). According to disease response to immunotherapy, the median overall survival was 3.6 months (95% CI, 2.0-5.2) for patients with progressive disease; it was not yet reached for those with disease control. The predictive accuracy of the 3D-pipeline was 82.5% (sensitivity 96%; specificity, 60%). The addition of baseline clinical factors increased the accuracy to 92.5% by improving specificity to 87%; the accuracy of other architectures ranged from 72.5% to 90%. Artificial Intelligence by 3D deep radiomics is a potential noninvasive biomarker for the prediction of disease control to ICIs in metastatic urothelial cancer and deserves validation in larger series. Copyright © 2021 Elsevier Inc. All rights reserved.