Systemic immunotherapeutics have been a clinical staple in the treatment of cancer, infectious diseases, organ and cell transplantation, autoimmunity, and allergies. Although their utility remains unquestioned, systemic administration of these drugs is associated with limited efficacy, significant adverse off-target effects, transient activity, and the requirement for frequent repeated dosing. To this end, recent technological advancements have provided novel means for sustained drug delivery to specific tissues and targeted localized approaches for immunotherapeutics. In this article, we present various cutting-edge platform technologies, including implants, multireservoir systems, and scaffolds encapsulating immunomodulatory agents for local administration. Examples of their application in cancer, cell transplantation, allergy, and infectious diseases are discussed, highlighting the potential of such systems for innovative immunomodulatory intervention.