Abstract: Disclosed are devices, systems and methods for in situ payload delivery via a degradable microneedle. In some aspects, a microneedle therapeutic payload delivery device includes a substrate; an activation particle; and one or more degradable microneedle structures coupled to the substrate and including a polymeric matrix structured to embed the activation microparticle and one or more therapeutic payloads, the one or more degradable microneedle structures each including an exterior wall spanning outward from a base surface and forming an apex at a terminus point of the exterior wall, wherein the polymeric matrix of a microneedle structure of the one or more degradable microneedle structures is degradable under an environmental parameter of a biofluid surrounding the microneedle structure to dissolve and allow the one or more therapeutic payloads and the activation particle to the surrounding biofluid.