<p>Buccal drug delivery offers a promising alternative to conventional oral administration, bypassing hepatic first-pass metabolism and gastric degradation that often limit drug bioavailability. This review explores the anatomical and physiological characteristics of the buccal mucosa that make it amenable to drug absorption, examining key formulation strategies including Quality by Design (QbD) principles, the use of mucoadhesive polymers, and permeation enhancers. The review further highlights recent advancements in buccal drug delivery systems, with a particular focus on nanotechnology-based approaches for enhancing the delivery of small as well as macromolecules and biologics. A comprehensive literature analysis demonstrates the potential of buccal delivery to improve therapeutic outcomes by leveraging the unique properties of the buccal mucosa and optimizing drug absorption through advanced formulation design and innovative technologies.</p> Graphical Abstract <p></p>