ONLINE COVER An artistic depiction showing the delivery of DNA molecules via acousto-thermal transfection into a human cell. This technique uses acoustic waves and localized heating to enhance the permeability of cell membranes. Previous methods faced difficult tradeoffs between efficiency and cell viability. Liu et al. propose an acoustothermal transfection approach combining acoustic and thermal effects on cells to realize the efficient delivery of multiple large plasmids while maintaining cell viability and easy scalability. This approach may become a powerful tool for future cellular and gene therapies.