Cholangiocarcinoma (CCA) is a highly aggressive malignancy of the biliary tract, characterized by late clinical presentation, limited therapeutic options, and pronounced inter- and intratumoral heterogeneity. Genomic and proteomic studies have uncovered recurrent alterations and etiological subgroups, yet these discoveries have translated poorly into consistent clinical benefit. A major reason is the lack of phosphoproteomic studies capable of capturing tumour-wide signaling programmes while accounting for spatial and patient-level variability.