Hepatocellular carcinoma with portal vein tumor thrombosis presents a significant therapeutic challenge due to its poor prognosis and limited treatment options. This review thoroughly examines diagnostic methods, including imaging techniques and classification systems such as the Japanese Vp and Cheng’s classifications, to aid in clinical decision-making. Treatment strategies encompass liver resection and liver transplantation, particularly living donor liver transplantation after successful downstaging, which have shown potential benefits in selected cases. Locoregional therapies, including hepatic arterial infusion chemotherapy, transarterial chemoembolization, transarterial radioembolization, and external beam radiation therapy, remain vital components of treatment. Recent advancements in systemic therapies, such as sorafenib, lenvatinib, and immune checkpoint inhibitors (e.g., atezolizumab plus bevacizumab) have demonstrated improvements in overall survival and progression-free survival. These developments underscore the importance of a multidisciplinary and personalized approach to improve outcomes for patients with hepatocellular carcinoma and portal vein tumor thrombosis.