In this editorial, we review the article by Ma and colleagues, published in the World Journal of Gastrointestinal Oncology . Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Although transarterial chemoembolization (TACE) has been used effectively for several years, particularly in patients with intermediate-stage HCC, the quest for the optimal combination therapy to enhance its efficacy and HCC treatment strategies persists. Combining TACE with tyrosine kinase inhibitors (TKIs) like sorafenib or lenvatinib has shown confusing results in improving both progression-free survival and overall survival. Similarly, combining TACE with immune checkpoint inhibitors (ICIs) has demonstrated potential efficacy by reshaping the tumor microenvironment and activating immune responses. Recent studies suggest combining TACE with TKIs and ICIs may offer synergistic effects. Additionally, combining TKIs and ICIs with other local treatments like microwave ablation or hepatic arterial infusion chemotherapy has shown promise in enhancing efficacy. However, more extensive prospective studies are needed to validate these findings. Overall, these combinations represent a promising direction in HCC management, emphasizing the need for further research to optimize treatment outcomes.