RNA modifications are crucial post-transcriptional regulators that influence RNA fate and various biological processes. This review discusses eight major RNA modifications—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—and their roles in cellular metabolism and immunometabolism. These modifications regulate glucose, lipid, amino acid, and mitochondrial metabolism, and are involved in immune responses. The review highlights the clinical implications of RNA modifications in metabolism-targeted therapy and immunotherapy, and discusses the potential of RNA modification-targeted agents in therapeutic applications. It also provides perspectives for future research in this field, emphasizing the need for methodological advancements and deeper mechanistic insights. The review underscores the importance of RNA modifications in both health and disease, and their potential as therapeutic targets.RNA modifications are crucial post-transcriptional regulators that influence RNA fate and various biological processes. This review discusses eight major RNA modifications—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—and their roles in cellular metabolism and immunometabolism. These modifications regulate glucose, lipid, amino acid, and mitochondrial metabolism, and are involved in immune responses. The review highlights the clinical implications of RNA modifications in metabolism-targeted therapy and immunotherapy, and discusses the potential of RNA modification-targeted agents in therapeutic applications. It also provides perspectives for future research in this field, emphasizing the need for methodological advancements and deeper mechanistic insights. The review underscores the importance of RNA modifications in both health and disease, and their potential as therapeutic targets.