Locally advanced pancreatic cancer (LAPC) accounts for approximately 40% of newly diagnosed pancreatic ductal adenocarcinoma cases and is characterized by extensive vascular invasion without distant metastases. Historically, treatment with chemotherapy alone has resulted in poor outcomes, with median overall survival ranging from 11 to 15 months. This study synthesizes the rapidly evolving multimodal treatment paradigm for LAPC. LAPC is typically defined by tumors larger than 4 cm or by greater than 180° encasement of major arterial structures, such as the superior mesenteric artery or celiac axis, often accompanied by venous involvement that is not amenable to reconstruction. Advances in neoadjuvant systemic therapy, including FOLFIRINOX or gemcitabine plus nab-paclitaxel, have enabled tumor downstaging in a subset of patients, with reported median overall survival approaching 20 months. Locoregional ablative strategies have further expanded treatment options. Irreversible electroporation preserves critical vascular and ductal structures and has demonstrated high technical success with overall survival ranging from 18 to 27 months when combined with chemotherapy. Radiofrequency ablation has also shown survival benefits, though with higher complication rates. Additional approaches, such as stereotactic body radiotherapy and peritoneal patch vascular reconstruction, have increased resectability in selected patients. Multimodal treatment strategies now allow conversion to resectable disease in 20–30% of cases and have been associated with substantial survival improvements, particularly in high-volume centers. Overall, the integration of systemic chemotherapy, ablative technologies, and advanced surgical techniques represents a paradigm shift in the management of LAPC, offering the potential to significantly extend survival while emphasizing the importance of multidisciplinary expertise and individualized patient care.