HCC is rare in the pediatric population, but is the second most common liver malignancy in children. Survival rates for primary unresectable HCC have been dismal. The objective of this study was to describe our experience with a multimodal approach for the management of unresectable HCC in two adolescent patients and to review the literature. Both patients are currently alive with no recurrence at 51 and 29 months post-transplant. Multimodality treatment involving chemotherapy with doxorubicin, cisplatin, and sorafenib; TACE; timely liver transplantation; and post-transplant therapy with sorafenib and mTOR inhibitors may help improve outcomes and prolong survival in pediatric patients with unresectable HCC.