Abstract <p>Otic drug delivery remains challenging due to anatomical and physiological barriers that restrict drug access to target sites, particularly within the middle and inner ear. This review aims to provide a focused and clinically relevant overview of current and emerging strategies to overcome these limitations. Key barriers, including the tympanic membrane, round window membrane, and blood–labyrinth barrier, are critically discussed in relation to disease-specific requirements in conditions such as otitis media, sudden sensorineural hearing loss, and Ménière’s disease. The limitations of conventional formulations and intratympanic administration are highlighted, particularly in terms of drug retention, permeability, and variability in therapeutic outcomes. Recent advances in nanocarrier systems (e.g., liposomes, and micelles) and biomaterial-based platforms (e.g., hydrogels and drug-eluting devices) are systematically evaluated, with emphasis on their ability to enhance drug penetration, prolong residence time, and achieve controlled release. The unique contribution of this review lies in integrating anatomical barriers, disease-specific therapeutic needs, and formulation strategies into a unified framework that links pharmaceutical design with clinical application, providing practical insights for the development of more effective and targeted otic therapies.</p> Graphical abstract <p></p>