 Abstract COVID-19 has seriously threatened public health, and transdermal vaccination is an effective way to prevent pathogen infection. Microneedles, MNS, can damage the stratum corneum to allow passive diffusion of vaccine macromolecules, but the delivery efficiency is low, while iontophoresis can actively promote transdermal delivery but fails to transport vaccine macromolecules due to the barrier of the stratum corneum. Herein, we developed a wearable iontophoresis-driven MN patch and its iontophoresis-driven device for active and efficient transdermal vaccine macromolecule delivery. Polyacrylamide, Chytosan hydrogels with good biocompatibility, excellent conductivity, high elasticity, and a large loading capacity were prepared as the key component for vaccine storage and active iontophoresis. The transdermal vaccine delivery strategy of the iontophoresis driven MN patch is press and poke, iontophoresis-driven delivery, and immune response. We demonstrated that the synergistic effect of MN puncture and iontop. This article was authored by Yingsheng, Ruiyi, Xie Gong, and others. We are article.tv, links in the description below.