The m⁶A modification is a prevalent and conserved internal modification in eukaryotic RNAs, particularly in higher eukaryotic cells. It is catalyzed by methyltransferases such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and removed by demethylases such as FTO and ALKBH5. It is recognized by m⁶A-binding proteins like YTHDF1/2/3, YTHDC1/2, IGF2BP1/2/3, and HNRNPA2B1. Recent studies have shown that m⁶A modification plays essential roles in both physiological and pathological conditions, especially in the initiation and progression of various human cancers. This review discusses how m⁶A RNA methylation influences the physiological and pathological progressions of hematopoietic, central nervous, and reproductive systems. It focuses on recent progress in identifying the biological functions and molecular mechanisms of m⁶A RNA methylation, its regulators, and downstream target genes during cancer progression in these systems. The review proposes that m⁶A RNA methylation could be a potential target for future cancer therapy. The m⁶A modification is involved in various biological processes, including RNA splicing, translation, stability, translocation, and high-level structure. The landscape of m⁶A in the transcriptome was first uncovered by next-generation sequencing, showing that an average of 3–5 m⁶A modifications occur in each mRNA out of one-third of mammalian total mRNAs. m6A modification has been identified on almost every type of RNA. Various methods have been developed to identify m6A sites, including PA-m6A-seq, miCLIP, and m6A-CLIP. The exact location of individual m6A sites can be identified with methods like m6A-REFseq and MAZTER-seq. The m⁶A modification is installed by the m6A methyltransferase complex, including METTL3, METTL14, WTAP, KIAA1429, METTL16, RBM15, and ZC3H13. It is removed by demethylases such as FTO and ALKBH5. The m6A reader proteins can recognize the m6A-modified RNAs, which are divided into different protein families. One class of direct m6A readers contains the YT521-B homology (YTH) domain, and several heterogeneous nuclear ribonucleoproteins (HNRNPs) fall into the other category, which mainly regulate alternative splicing or processing of target transcripts. IGF2BP1/2/3 and eIF3 belong to another subfamily. DifferentThe m⁶A modification is a prevalent and conserved internal modification in eukaryotic RNAs, particularly in higher eukaryotic cells. It is catalyzed by methyltransferases such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and removed by demethylases such as FTO and ALKBH5. It is recognized by m⁶A-binding proteins like YTHDF1/2/3, YTHDC1/2, IGF2BP1/2/3, and HNRNPA2B1. Recent studies have shown that m⁶A modification plays essential roles in both physiological and pathological conditions, especially in the initiation and progression of various human cancers. This review discusses how m⁶A RNA methylation influences the physiological and pathological progressions of hematopoietic, central nervous, and reproductive systems. It focuses on recent progress in identifying the biological functions and molecular mechanisms of m⁶A RNA methylation, its regulators, and downstream target genes during cancer progression in these systems. The review proposes that m⁶A RNA methylation could be a potential target for future cancer therapy. The m⁶A modification is involved in various biological processes, including RNA splicing, translation, stability, translocation, and high-level structure. The landscape of m⁶A in the transcriptome was first uncovered by next-generation sequencing, showing that an average of 3–5 m⁶A modifications occur in each mRNA out of one-third of mammalian total mRNAs. m6A modification has been identified on almost every type of RNA. Various methods have been developed to identify m6A sites, including PA-m6A-seq, miCLIP, and m6A-CLIP. The exact location of individual m6A sites can be identified with methods like m6A-REFseq and MAZTER-seq. The m⁶A modification is installed by the m6A methyltransferase complex, including METTL3, METTL14, WTAP, KIAA1429, METTL16, RBM15, and ZC3H13. It is removed by demethylases such as FTO and ALKBH5. The m6A reader proteins can recognize the m6A-modified RNAs, which are divided into different protein families. One class of direct m6A readers contains the YT521-B homology (YTH) domain, and several heterogeneous nuclear ribonucleoproteins (HNRNPs) fall into the other category, which mainly regulate alternative splicing or processing of target transcripts. IGF2BP1/2/3 and eIF3 belong to another subfamily. Different