Vaccines are developed to prevent acute infectious diseases, but emerging evidence suggests that some vaccines, like the influenza vaccine, may additionally help reduce the risk of chronic disease development and progression. As federal policies shift toward chronic disease prevention, understanding vaccines’ broader impact is critical. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, conducting article searches using PubMed, Web of Science, and Embase databases. We included all peer-reviewed studies from 2000 to 2025 and excluded those that were non-human research and non-English-translated. Perplexity AI was used to supplement searches and Covidence for screening and review processes. Two reviewers independently conducted article screening and data extraction. Discrepancies were resolved by consensus. Of 703 unique articles produced by our searches, 88 articles met inclusion and exclusion criteria; 8 were randomized trials, 49 were observational studies, 14 were systematic reviews, and 15 were guidelines or reviews. The influenza vaccine has been shown to help prevent incidence, morbidity, and mortality of cardiovascular disease (e.g., strokes, myocardial infarction, heart failure, coronary artery disease, and hypertension). Additionally, the influenza vaccine is associated with decreased chronic obstructive pulmonary disease (COPD) exacerbations and a lower risk of chronic fatigue syndrome, chronic kidney disease, dementia, and potentially T1D, cancer, and Parkinson’s disease. Beyond acute infectious disease prevention, the influenza vaccine has protective effects against chronic diseases and their progression. Strategies to improve vaccine uptake and address barriers are essential to maximize long-term public health benefits. This work will continue further with a series of systematic reviews, including other Centers for Disease Control and Prevention (CDC) adult-recommended vaccinations.