The physiology and anatomy of the site at which hybrid hydrogels are administered must be considered for a successful sustained release of active molecules. As an example, controlled delivery to the myocardium of SS-31 (an antioxidant peptide) and S1P (a proangiogenic lipid), was achieved with a Gel/drug-loaded liposome hybrid hydrogel whose properties were finely tuned to achieve injectability, an elastic modulus comparable to that of the natural myocardium as well as conductive properties. The latter were obtained through the coupling of poly-3amino-4-methoxybenzoic acid moieties to the Gel matrix, which facilitated the transmission of electrical signals and played a pivotal role in restoring cardiac function in a myocardial infarct model. Softness and adhesiveness were instead required for hydrogels designed to treat ocular fungal keratitis. To meet these criteria, a combination of quaternized CS (HTCC) and GO was used to form a flexible material via multiple hydrogen bonding. This material could be cast on contact lens molds, creating an innovative ophthalmic dosage form. The incorporation of Ag NPs and voriconazole-loaded GO into the hydrogel ensured effective antibacterial and antifungal activity, leading to the resolution of keratitis in a rabbit model within 7 days. The system presented an initial drug burst release, enabling therapeutic concentrations to be achieved even with a limited amount of diffusion medium, as is the case in the eye. The drug was then released progressively, underlining the potential of the contact lens as a support for sustained drug delivery.