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Advancements in micro-resolution 3D printers have significantly facilitated the development of highly complex mass-producible drug delivery platforms. Conventionally, due to the limitations of micro-milling machineries, dissolvable microneedles (MNs) are mainly fabricated in cone-shaped geometry with limited drug delivery accuracy. Herein, to overcome the limitations of conventional MNs, a novel projection micro-stereolithography 3D printer-based self-locking MN for precise skin insertion, adhesion, and transcutaneous microdose drug delivery is presented. The geometry of self-locking MN consists of a sharp skin-penetrating tip, a wide skin interlocking body, and a narrow base with mechanical supports fabricated over a flexible hydrocolloid patch to improve the accuracy of skin penetration into irregular surfaces. Melanoma, a type of skin cancer, is selected as the model for the investigation of self-locking MNs due to its irregular and uneven surface. In vivo immunotherapy efficacy is evaluated by integrating SD-208, a novel transforming growth factor-β (TGF-β) inhibitor that suppresses the proliferation and metastasis of tumors, and anti-PD-L1 (aPD-L1 Ab), an immune checkpoint inhibitor that induces T cell-mediated tumor cell death, into self-locking MNs and comparing them with intratumoral injection. Evaluation of (aPD-L1 Ab)/SD-208 delivery effectiveness in B16F10 melanoma-bearing mice model confirms significantly improved dose efficacy of self-locking MNs compared with intratumoral injection., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)