Nature Reviews Cancer, Published online: 08 December 2025; doi:10.1038/s41568-025-00889-6In this Review Luo, Kharas and Jaffrey outline how N6-methyladenosine (m6A) RNA modification affects RNA stability, translation, splicing and immune responses to influence cancer biology. They discuss emerging evidence on how m6A may influence cancer metabolic reprogramming and outline the challenges and opportunities of targeting m6A writers, erasers and readers for cancer therapy.