Adjuvants are crucial components of vaccines, enhancing immune responses and improving vaccine efficacy. Recent advances in immunology and vaccine development have led to the design of novel adjuvants with improved safety and efficacy profiles. This review examines the mechanistic insights and clinical applications of adjuvants in modern vaccine design, highlighting recent advances and future directions. Findings from this study show that adjuvants stimulate innate immune responses, enhancing antigen presentation and activation of adaptive immunity. Toll-like receptor agonists, squalene-based adjuvants, and particulate adjuvants are among the most promising classes of adjuvants. Clinical trials have demonstrated the safety and efficacy of adjuvanted vaccines against infectious diseases, such as influenza and human papillomavirus, and cancer. Adjuvants have also shown potential in improving vaccine responses in vulnerable populations, including the elderly and immunocompromised individuals. Adjuvants play a vital role in modern vaccine design, enabling the development of effective and safe vaccines. Mechanistic insights into adjuvant action have informed the rational design of novel adjuvants, with improved safety and efficacy profiles. Continued research into adjuvant development will be crucial for addressing emerging infectious diseases and improving global health outcomes.