With rapid developments in medical science and technology, vaccination has become the key to solving public health problems. Various diseases can be prevented by vaccination, which mimic a disease by using a small part of the causal organism-also called an antigen-to stimulate the specific immune response to defend the host against the disease. The interaction between antigens and antigen-presenting cells (APCs) affects the efficacy of a vaccine. Adjuvants are crucial components of vaccines, optimizing the process of antigen phagocytosis by the APCs to some extent. However, many vaccinations fail during application in clinical trials owing to drawbacks of some antigens and adjuvants, such as immunogenicity and high degradability. Owing to rapid developments in the payload, targeted delivery and controllable release of drug delivery systems, they may have the potential to improve vaccines. In our review, we discuss multiple delivery systems and their role in vaccines and discuss how the major physical properties of delivery systems ultimately affect the success of vaccines, such as size, morphology, surface charge and elasticity.