Hepatocellular carcinoma (HCC) is the most common liver cancer and presents various degrees of aggressiveness. In this case study, we reported the management of an aggressive HCC patient who was a young immigrant from a hepatitis B endemic country with locally advanced HCC with portal involvement at presentation. Patient was initially managed with Yttrium-90 (Y-90) instillation, then systemic treatment when he had disease progression. Despite multiple lines of systemic treatments, patient continued to progress and developed significant cardiac involvement and pulmonary tumor thromboemboli. His course of treatment was further complicated by hemoptysis, presumably from hemorrhagic tumor thromboemboli. Patient became ineligible for systemic treatment due to the risk of hemoptysis, thus, subsequently managed with a course of palliative radiotherapy. Unfortunately, patient developed hemorrhagic shock, cardiac failure, and septic shock during radiation treatment and expired shortly afterward. In this case report, we discussed multi-modal treatments, including Y-90, systemic treatment, and radiotherapy, in managing complicated and aggressive HCC. We also reported risk factors, prognostic factors, efficacy of Y-90 instillation and the necessity of a personalized treatment approach. In conclusion, there is no consensus on managing patients with metastatic HCC with cardiac and pulmonary involvement currently. Treatment modalities are often highly personalized and require multi-disciplinary discussion.