Ocular nanomedicines for precise targeted delivery and controlled release in clinical application have expanded. However, developing materials that harmonize with biomechanical properties of various anatomical regions in the eye remains neglected. For instance, biomaterials engineered to mimic the cornea’s biomechanical and optical properties can achieve superior integration with ocular surface structures, thereby reducing corneal trauma and extending nanomaterial persistence. Beyond the corneal surface, biomechanically optimized strategies that consider the viscoelasticity and structural integrity of the retina and choroid can significantly improve intraocular drug delivery. Nanomaterials with dynamic biomechanical responsiveness, such as intraocular pressure (IOP)-sensitive behavior, enable controlled drug release and enhance therapeutic efficacy in glaucoma management. Notably, nanomaterials with mechanical stiffness compatible with ocular biomechanics can preserve tissue integrity, stabilize the globe structure, and mitigate trauma-related complications. This review synthesizes current understanding of the biomechanical properties of ocular tissues and provides structural perspectives to inform the development of next-generation nanomaterials for ophthalmic use. We envision that these insights will foster translational innovation and advance biomechanically informed strategies in ocular nanomedicine.