The regulation of gene expression is pivotal in cancer development, with increasing emphasis on epigenetic modifications such as RNA methylation. N6-methyladenosine (m6A), the most abundant RNA modification, critically impacts RNA function and stability. METTL16, an m6A methyltransferase or “writer”, is essential in this modification process. Aberrant expression of METTL16 is closely linked to cancer cell proliferation, invasion, metastasis, and drug resistance, through modulation of RNA metabolism. Despite extensive research on RNA-modifying enzymes, the specific mechanisms and roles of METTL16 in cancer remain poorly understood. This review provides a detailed examination of METTL16's functions and regulatory mechanisms in cancer, emphasizing its m6A-dependent and m6A-independent roles in regulating RNA stability and function. Furthermore, it proposes that targeting METTL16 represents a promising avenue for cancer therapy.