The development of effective vaccines requires a rational design that considers the interaction between antigens, their vectors, and the immune system in addition to the activation of pathways that induce a safe and specific immune response. The efficacy of a vaccine formulation depends on the nature of the antigen, the protection offered by the delivery system, the ability to potentiate the immune response, and the precise release of the immunogen. Carrier systems such as lipid nanoparticles, polymers, exosomes, and microorganisms can be functionalized by chemical, physical, or biological methods to generate selective and improved biodistribution profiles. These methods enhance interaction with target cells, thereby improving immunological efficacy. The conjugation of specific ligands or the modification of parameters such as shape, charge, and size of vectors can enhance the specificity, stability, and efficiency of antigen transport to cellular compartments, thereby facilitating a robust immune response. This study examines modifications in vaccine delivery systems, focusing on biomolecules and physicochemical changes that enhance antigen presentation. Additionally, we examine innovative methods, including microneedles, electroporation, and needle-free systems that show potential for enhancing the immune response.