This review article explores the role of RNA modifications in cellular metabolism and their implications for metabolism-targeted therapy and immunotherapy. RNA modifications, such as N6-methyladenosine (m6A), N6,2′-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing, are crucial in post-transcriptional regulation. These modifications influence various biological processes and cellular phenotypes by altering RNA fate, including splicing, trafficking, degradation, and translation. The article highlights the regulatory roles of these modifications in glucose, lipid, amino acid, and mitochondrial metabolism, as well as their impact on immunometabolism and immune responses. It also discusses the clinical implications of RNA modifications in metabolism-targeted therapy and immunotherapy, emphasizing the need for further research in methodological requirements, mechanistic insights, and therapeutic applications. The review provides a comprehensive overview of the current understanding of RNA modifications and their significance in cellular metabolism, offering insights into potential therapeutic strategies.This review article explores the role of RNA modifications in cellular metabolism and their implications for metabolism-targeted therapy and immunotherapy. RNA modifications, such as N6-methyladenosine (m6A), N6,2′-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing, are crucial in post-transcriptional regulation. These modifications influence various biological processes and cellular phenotypes by altering RNA fate, including splicing, trafficking, degradation, and translation. The article highlights the regulatory roles of these modifications in glucose, lipid, amino acid, and mitochondrial metabolism, as well as their impact on immunometabolism and immune responses. It also discusses the clinical implications of RNA modifications in metabolism-targeted therapy and immunotherapy, emphasizing the need for further research in methodological requirements, mechanistic insights, and therapeutic applications. The review provides a comprehensive overview of the current understanding of RNA modifications and their significance in cellular metabolism, offering insights into potential therapeutic strategies.