Several strategies, including chemotherapy and radiotherapy, have improved therapeutic outcomes among cancer patients in clinical practice. However, due to their heterogeneity, cancer cells frequently display primary or acquired therapeutic resistance, thereby resulting in treatment failure. The mechanisms underlying cancer therapeutic resistance are complex and varied. Among them, N6-methyladenosine (m6A) RNA modification has gained increasing attention as a potential determinant of therapy resistance within various cancers. In this review, we primarily describe evidence for the effect of the m6A epitranscriptome on RNA homeostasis modulation, which has been shown to alter multiple cellular pathways in cancer research and treatment. Additionally, we discuss the profiles and biological implications of m6A RNA methylation, which is undergoing intensive investigation for its effect on the control of therapeutic resistance.