Stem cells’ secretome contains biomolecules that are ready to give therapeutic activities. However, the biomolecules should not be administered directly because of their in vivo instability. They can be degraded by enzymes or seep into other tissues. There have been some advancements in localized and stabilized secretome delivery systems, which have increased their effectiveness. Fibrous, in situ, or viscoelastic hydrogel, sponge-scaffold, bead powder/ suspension, and bio-mimetic coating can maintain secretome retention in the target tissue and prolong the therapy by sustained release. Porosity, young’s modulus, surface charge, interfacial interaction, particle size, adhesiveness, water absorption ability, in situ gel/film, and viscoelasticity of the preparation significantly affect the quality, quantity, and efficacy of the secretome. Therefore, the dosage forms, base materials, and characteristics of each system need to be examined to develop a more optimal secretome delivery system. This article discusses the clinical obstacles and potential solutions for secretome delivery, characterization of delivery systems, and devices used or potentially used in secretome delivery for therapeutic applications. This article concludes that secretome delivery for various organ therapies necessitates the use of different delivery systems and bases. Coating, muco-, and cell-adhesive systems are required for systemic delivery and to prevent metabolism. The lyophilized form is required for inhalational delivery, and the lipophilic system can deliver secretomes across the blood-brain barrier. Nano-sized encapsulation and surface-modified systems can deliver secretome to the liver and kidney. These dosage forms can be administered using devices such as a sprayer, eye drop, inhaler, syringe, and implant to improve their efficacy through dosing, direct delivery to target tissues, preserving stability and sterility, and reducing the immune response.