Transdermal vaccine delivery using microneedle (MN) technology represents a groundbreaking approach in immunization strategies. This comprehensive review examines the latest advancements in MN-based vaccine delivery systems, focusing on their design principles, immunological mechanisms, and clinical applications. We systematically analyze various MN platforms including dissolving microneedles, coated microneedles, and hydrogel-forming microneedles for their efficacy in delivering both conventional and novel vaccine candidates. The discussion encompasses antigen stability during fabrication, immune response optimization, and large-scale manufacturing considerations. Special attention is given to the unique advantages of MN systems for pandemic response, including thermostability, self-administration potential, and reduced medical waste. Furthermore, we evaluate the clinical translation progress through analysis of completed and ongoing human trials, regulatory considerations, and commercialization challenges. The integration of MN technology with emerging vaccine platforms offers promising opportunities for revolutionizing global immunization programs.