The creation of vaccines has revolutionized several aspects of the game in the fight against transmissible diseases, protecting countless individuals around the globe. Several vaccines against potentially fatal diseases such as diphtheria, pertussis, polio, measles, tetanus, influenza, and smallpox have significantly reduced disease risks and successfully immunized individuals against these serious health threats. The immune response generated by vaccination plays a crucial role in mitigating disease risks by stimulating the production of specific antibodies targeting the relevant pathogens. However, the efficacy of vaccines can vary among communities and people due to several factors, including heredity, age, sex, and preexisting health conditions. The multitude of microbes that call the human digestive tract the microbiota have a pivotal role in regulating immunological reactions to immunization, according to mounting data from both experimental models and research trials. Nutritional supplementation with beneficial microbes, such as probiotic bacteria, has been shown to have immune-related benefits, including enhancements of immune system responses, and has the potential to modify the variety that makes up the microbiota. The effectiveness of vaccines can be enhanced by using probiotics, which work by fostering a balanced gut microbiome. New research reveals that the immune response can be influenced by both live and dormant probiotic bacteria, as well as postbiotics, which are byproducts of the metabolism of probiotics. These substances have immunomodulatory functions and are essential in regulating how the immune system reacts to vaccines. This review aims to summarize the available research, explore the possible immune system functions that could explain these effects, and ultimately speculate about how postbiotics, aimed at the biotic microbiota, could improve the efficacy of vaccines. The review further addresses postbiotics' challenges, regulatory aspects, and future directives for biotherapeutic products that could enhance vaccine efficacy and be tailored for personalized treatments.