<p>mRNA vaccines benefit from rapid design, scalable manufacturing and strong safety profiles, and they are being preclinically and clinically explored for various infectious diseases, cancer and autoimmune disorders. However, global access to mRNA vaccines remains limited by technical, logistical, economic, regulatory and ethical challenges. In this Review, we discuss the current mRNA vaccine landscape, from approved products to emerging candidates, and outline key barriers to equitable access. We highlight engineering strategies to address these barriers, including thermostability improvements, alternative administration routes, new delivery systems and alternative RNA platforms, such as self-amplifying and circular RNA, as well as the integration of artificial intelligence- and machine learning-based design and optimization. We also discuss the regulatory, ethical and social dimensions of vaccine deployment, as well as the importance of building public trust and community engagement. Coordinated technical and policy advances are essential to remove barriers, enhance access and advance global health equity.</p>