Microneedles have been explored as a novel way of delivering active ingredients into the skin. They have various advantages, such as quick and efficient drug delivery, mechanical stability, minimal pain, variable capacity and easy use. Microneedles are enabled for the delivery of vaccine, peptides, medicinal components and in cosmetology, which couldn't go unnoticed. The novel approaches in the transdermal drug delivery system have increased the efficiency of drug delivery into the skin by crossing the skin barriers. This platform has a wide range of applications and can also be used to deliver non-transdermal biomedicals. The variety in the design of microneedles has demanded similar diversity in their methods of fabrication; micro molding and drawing lithography may be useful methods. There are different types of polymers and materials for the fabrication of microneedles. Several synthetic and natural materials are used in the fabrication of microneedles. Unique shapes, materials, and mechanical properties are modified for organ-specific applications in microneedle engineering. In this review, we discuss several factors and their roles to cross the biological barriers for transdermal drug delivery in various sites, such as in ocular, vascular, oral, and mucosal tissue. Additionally, this article highlights the future scope of transdermal drug delivery systems through microneedles.