Simple SummaryPancreatic cancer is a highly aggressive disease associated with poor clinical outcomes. It is the seventh leading cause of cancer-related death worldwide. Due to the lack of obvious signs and symptoms until advanced disease, establishing an early diagnosis is often difficult. EUS is the imaging modality of choice to establish a diagnosis of pancreatic cancer. However, over the years, EUS has evolved to have therapeutic applications in the management of pancreatic cancer. EUS-guided fine needle injection of anti-tumoral agents, EUS-guided radiotherapy, and EUS-guided ablation techniques have become vital tools for endoscopic oncologists, especially in the management of locally advanced pancreatic cancer. These EUS-guided techniques offer high efficacy and demonstrate an excellent safety profile. However, they have not yet become routine practice due to the lack of long-term efficacy outcomes. Hence, additional studies are needed to investigate the long-term clinical outcomes and establish standardized procedural protocols for these techniques.AbstractPancreatic cancer is a highly lethal disease with an aggressive clinical course. Patients with pancreatic cancer are usually asymptomatic until significant progression of their disease. Additionally, there are no effective screening guidelines for pancreatic cancer in the general population. This leads to a delay in diagnosis and treatment, resulting in poor clinical outcomes and low survival rates. Endoscopic Ultrasound (EUS) is an indispensable tool for the diagnosis and staging of pancreatic cancer. In the modern era, with exponential advancements in technology and device innovation, EUS is also being increasingly used in a variety of therapeutic interventions. In the context of pancreatic cancer where therapies are limited due to the advanced stage of the disease at diagnosis, EUS-guided interventions offer new and innovative options. Moreover, due to their minimally invasive nature and ability to provide real-time images for tumor localization and therapy, they are associated with fewer complication rates compared to conventional open and laparoscopic approaches. In this article, we detail the most current and important therapeutic applications of EUS for pancreatic cancer, namely EUS-guided Fine Needle Injections, EUS-guided Radiotherapy, and EUS-guided Ablations. Furthermore, we also discuss the feasibility and safety profile of each intervention in patients with pancreatic cancer to provide gastrointestinal medical oncologists, radiation and surgical oncologists, and therapeutic endoscopists with valuable information to facilitate patient discussions and aid in the complex decision-making process.