Herein, we provide an overview on the current knowledge regarding the predictive biomarkers of the response to ICIs in advanced BTCs, especially focusing on the role of programmed death-ligand 1 (PD-L1) expression, tumor mutational burden (TMB), mismatch repair deficiency (dMMR), high microsatellite instability (MSI-H), and DNA damage repair (DDR) gene mutations in this setting. This evidence concerns the gene CD274 and neoplasm.