Metabolic reprogramming in the tumor microenvironment of liver cancer is a critical factor in tumor progression and immune evasion. The liver, essential for metabolic homeostasis, undergoes significant metabolic changes in liver cancer, leading to dysregulated cellular metabolism that promotes tumor growth and immune suppression. This review explores the metabolic interactions between liver cancer cells and immune cells, highlighting how metabolic reprogramming impacts the immune microenvironment and the efficacy of immunotherapy. The gut-liver axis plays a crucial role in modulating immune surveillance and escape, offering novel therapeutic opportunities. Liver cancer, particularly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), is influenced by various risk factors, including viral infections, obesity, and metabolic disorders. Metabolic reprogramming in liver cancer cells leads to altered energy production, nutrient utilization, and immune cell function, creating an immunosuppressive environment. Key metabolic pathways, such as aerobic glycolysis, lipid metabolism, and amino acid metabolism, are dysregulated in liver cancer, contributing to tumor progression and resistance to therapy. Metabolic interactions between tumor cells and the tumor microenvironment (TME) are complex, with nutrient competition and oncometabolite production playing significant roles in immune evasion. Lactate, lipid metabolites, and amino acids modulate immune cell function, promoting tumor growth and suppressing immune responses. The gut microbiota also influences liver cancer progression through the gut-liver axis, affecting immune cell function and therapeutic outcomes. Targeting metabolic pathways in liver cancer is a promising approach to enhance immunotherapy. Metabolic reprogramming of immune cells can be leveraged to improve anti-tumor immunity. The gut microbiome's role in liver cancer progression and immunotherapy response is increasingly recognized, with potential therapeutic strategies emerging from modulating microbial metabolites. In conclusion, understanding and targeting metabolic reprogramming in liver cancer is essential for developing effective therapies. The interplay between tumor metabolism, immune cells, and the gut microbiome offers new avenues for improving treatment outcomes in liver cancer. Further research is needed to fully elucidate these mechanisms and translate findings into clinical applications.Metabolic reprogramming in the tumor microenvironment of liver cancer is a critical factor in tumor progression and immune evasion. The liver, essential for metabolic homeostasis, undergoes significant metabolic changes in liver cancer, leading to dysregulated cellular metabolism that promotes tumor growth and immune suppression. This review explores the metabolic interactions between liver cancer cells and immune cells, highlighting how metabolic reprogramming impacts the immune microenvironment and the efficacy of immunotherapy. The gut-liver axis plays a crucial role in modulating immune surveillance and escape, offering novel therapeutic opportunities. Liver cancer, particularly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), is influenced by various risk factors, including viral infections, obesity, and metabolic disorders. Metabolic reprogramming in liver cancer cells leads to altered energy production, nutrient utilization, and immune cell function, creating an immunosuppressive environment. Key metabolic pathways, such as aerobic glycolysis, lipid metabolism, and amino acid metabolism, are dysregulated in liver cancer, contributing to tumor progression and resistance to therapy. Metabolic interactions between tumor cells and the tumor microenvironment (TME) are complex, with nutrient competition and oncometabolite production playing significant roles in immune evasion. Lactate, lipid metabolites, and amino acids modulate immune cell function, promoting tumor growth and suppressing immune responses. The gut microbiota also influences liver cancer progression through the gut-liver axis, affecting immune cell function and therapeutic outcomes. Targeting metabolic pathways in liver cancer is a promising approach to enhance immunotherapy. Metabolic reprogramming of immune cells can be leveraged to improve anti-tumor immunity. The gut microbiome's role in liver cancer progression and immunotherapy response is increasingly recognized, with potential therapeutic strategies emerging from modulating microbial metabolites. In conclusion, understanding and targeting metabolic reprogramming in liver cancer is essential for developing effective therapies. The interplay between tumor metabolism, immune cells, and the gut microbiome offers new avenues for improving treatment outcomes in liver cancer. Further research is needed to fully elucidate these mechanisms and translate findings into clinical applications.