In recent years, cancer genomic medicine centered on comprehensive genome profile (CGP) analysis has become widely used in the field of pancreatic cancer. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has played an important role in pancreatic cancer, and recently, more EUS-TA tissue samples are considered for CGP analysis. Differences exist between the Oncoguide NCC Oncopanel System and Foundation One CDx Cancer Genome Profile, which are CGP tests approved by insurance programs in Japan, including the analysis criteria, optimal needle selection for meeting these criteria, and puncture target. It is important to understand not only the specimen collection factors, but also the specimen processing factors that can increase the success rate of CGP testing. Furthermore, cancer genome medicine is expected to enter an era of increasing turbulence in the future, and endoscopists need to respond flexibly to these changes. Herein, we review the current status of cancer genome medicine in pancreatic and biliary tract cancers and cancer gene panel testing using EUS-TA.