Biliary tract cancers are now seeing transformative therapies that enhance patient outcomes.

• Chemo-immunotherapy is the new first-line standard of care.
• Targeted therapies, especially for intrahepatic cholangiocarcinoma with FGFR2 fusions, show high response rates with drugs like pemigatinib and futibatinib.
• IDH1-mutant cholangiocarcinoma can be treated effectively with ivosidenib.

Surgeons should prioritize biomarker testing to personalize treatment strategies and overcome barriers in accessibility and resistance.

• HER2-targeted options are also promising for patients with HER2 amplification.