Transdermal microneedle patches represent a transformative advancement in vaccine delivery technology, offering painless, minimally invasive immunization through controlled antigen administration into skin layers enriched with antigen-presenting cells. These micron-scale devices circumvent limitations of conventional needle-syringe vaccination, including cold-chain dependence, needle-phobia, sharps disposal hazards, and requirement for trained healthcare personnel. This review comprehensively examines the design principles, fabrication methodologies, and immunological mechanisms underlying microneedle-based vaccine delivery systems. Various microneedle architectures are analyzed, including solid, coated, dissolving, hollow, and hybrid configurations, each offering distinct advantages for antigen stability, release kinetics, and immunogenicity enhancement. Emphasis is placed on materials engineering, manufacturing scalability, dose precision, and immune activation pathways mediated by Langerhans cells and dermal dendritic cells in skin immunization. Clinical applications spanning viral, bacterial, and subunit vaccines demonstrate comparable or superior immunological responses relative to intramuscular administration, with particular relevance for pandemic preparedness, mass immunization campaigns, and vulnerable populations. Despite promising preclinical and clinical data, challenges persist regarding manufacturing standardization, regulatory frameworks, long-term stability, and global deployment logistics. Future innovations integrating adjuvant incorporation, thermostable formulations, and multi-antigen delivery promise to establish microneedle patches as mainstream vaccination platforms, advancing patient compliance, healthcare accessibility, and immunization coverage worldwide.