Hepatocellular carcinoma (HCC) is a prevalent and lethal cancer, often diagnosed at advanced stages where traditional treatments such as surgical resection, liver transplantation, and locoregional therapies provide limited benefits. Hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment modality for advanced HCC, enhancing anti-tumor efficacy through targeted drug delivery while minimizing systemic side effects. However, the heterogeneous nature of HCC leads to variable responses to HAIC, highlighting the necessity for reliable predictive indicators to tailor personalized treatment strategies. This review explores the factors influencing HAIC success, including patient demographics, tumor characteristics, biomarkers, genomic profiles, and advanced imaging techniques such as radiomics and deep learning models. Additionally, the synergistic potential of HAIC combined with immunotherapy and molecular targeted therapies is examined, demonstrating improved survival outcomes. Prognostic scoring systems and nomograms that integrate clinical, molecular, and imaging data are discussed as superior tools for individualized prognostication compared to traditional staging systems. Understanding these predictors is essential for optimizing HAIC efficacy and enhancing survival and quality of life for patients with advanced HCC. Future research directions include large-scale prospective studies, integration of multi-omics data, and advancements in artificial intelligence to refine predictive models and further personalize treatment approaches.