Abstract: Provided herein is a transdermal system for direct local co-delivery of immune checkpoint inhibitor and chemotherapeutic agent by microneedles for synergistic immuno-chemotherapy. Provided herein are lipid-coated nanoparticles and their use to facilitate the drug release and tumor-targeting. Also provided herein is a method of treatment of cancer and other disorder using the system. The present treatment method boost immune response in the tumor microenvironment and enhance the inhibition efficiency for tumor cells and decrease systemic toxicity in a subject unresponsive to systemic therapy.