Intrahepatic cholangiocarcinoma (ICC) is a malignancy with an insidious onset and extremely high mortality, often resulting in the inability to perform radical surgery due to vascular invasion and metastasis. The middle hepatic vein (MHV), located adjacent to the left and right hepatic veins and the second hepatic hilum, is an essential component of the hepatic vascular system. Patients with ICC involving the MHV face significant treatment challenges, and there is considerable debate regarding the optimal treatment decisions. Conversion therapy has provided new hope for patients with initially unresectable ICC, particularly for those with MHV invasion, who have an urgent need for such treatment. This article combines relevant research findings and clinical experience of the authors' team to discuss several challenges in conversion therapy for ICC with MHV invasion, aiming to provide reference for the clinical management of these patients.