Shubham Pant, MD, MBBS; Haley Ellis, MD; Amit Mahipal, MD; and Darshil Shah, MD, MPH, examine the evolving landscape of biliary tract cancer management, covering critical aspects from initial prognosis communication through biomarker testing strategies, first-line immunotherapy combinations, and the emergence of HER2-targeted therapies, while highlighting recent clinical trial data and ongoing challenges in optimizing patient outcomes.