This chapter offers an extensive review of polymer-based microneedles (MNs) as an important technique for transdermal drug delivery systems (TDDS). Polymer MNs, produced from biocompatible, biodegradable, and/or synthetic polymers, have numerous benefits in TDDS, such as facile manufacture, customizable drug release profiles, and reduced invasiveness. MNs could efficiently penetrate tissues, preserving continuous contact without injury while generating a strong adhesive force. The design concepts and materials choice for polymer-based MNs emphasize the characteristics of frequently utilized polymers, including poly(lactic-co-glycolic acid) (PLGA), polyvinyl alcohol (PVA), cellulose, carboxymethyl cellulose and hydrogel-based materials. Cellulose has garnered considerable attention in the production of MNs due to its distinctive qualities, such as high mechanical strength, low cost, and ease of fabrication. These polymers can be customized for several therapeutic uses, facilitating the efficient delivery of various drugs, from small organic molecules to large biomacromolecules. The study also addresses MNs production techniques like micro-molding, drawing lithography, 3D printing, and solvent casting, as well as the mechanical and drug-delivery efficiency properties of polymer MNs, such as insertion ability and skin penetration. Finally, it evaluates the use of cellulose/organic polymer-based MNs in a variety of therapies, such as vaccinations, drug/protein delivery, and pain management. This chapter highlights the promise of polymer-based MNs for TDDS by breaking down existing barriers and providing a less intrusive alternative to injection-based therapy.