Biliary tract cancers (BTC) constitute a highly heterogeneous group of malignancies within the digestive system, characterized by marked biological aggressiveness. Pre-operative treatment can downstage tumors and enhance resectability, whereas post-operative therapy aims to eradicate occult micrometastases and delay relapse. Gemcitabine-based chemotherapy remains the therapeutic backbone, yet recent trials evaluating multimodal regimens combining cytotoxic agents with immune-checkpoint inhibitors or tyrosine-kinase inhibitors in neoadjuvant, conversion, and adjuvant settings have shown encouraging improvements in R0 resection rates and survival outcomes. Future studies should standardize peri-operative immuno-combination protocols and response-assessment metrics, implement personalized strategies grounded in molecular subtyping and immune profiling, harmonize definitions of “borderline resectable” and “unresectable”, and develop predictive biomarkers to identify patients most likely to benefit and to optimize dosing sequences.