Many of the factors that play a critical role in the promotion of strong immune responses, including vaccine formula, adjuvant, production process, administration method, and directing of antigen to immune cells are interrelated. For the past two decades, nanotechnology has used in designing the new generation of adjuvants. The nano adjuvants apply in targeted delivery and controlled release of antigen to induce the more strengthen cellular and humoral immune responses. A comprehensive literature search concerning nano adjuvants and enhancing the immune system was conducted using articles published in recent years. The size and surface characteristics of nanoparticles are the dominant factors in controlling their behavior in biological transmission, tissue and cell uptake, and inducing immune reactions. Understanding the physicochemical properties of nanoparticles and their quality is essential because these elements may lead to dynamic changes in the biological conditions, such as affecting cells during absorption and transmission. Nano adjuvants provide great opportunities for improving immune responses through mucosal immunization. For clinical approval of nano-based formulations of antigen and adjuvant, some optimizations need to be taken as pointed out in this review.