As the most abundant internal mRNA modification in eukaryotic cells, N 6 -methyladenosine (m 6 A) has emerged as an important regulator of gene expression and has a profound impact on cancer initiation and progression. mRNA m 6 A modification is regulated by m 6 A methyltransferases, demethylases and reader proteins to fine tune gene expression at the post-transcriptional level. The most well-studied m 6 A methyltransferase, METTL3, plays critical roles in regulating gene expression and affecting the outcome of various cancers. In this review, we discuss the multifaceted roles of METTL3 in regulating specific molecular signaling pathways in different types of cancers and the recent progress on how METTL3 impacts the tumor immune microenvironment. Finally, we discuss future directions and the potential for therapeutic targeting of METTL3 in cancer treatment.