We performed a systematic literature review in PubMed and Embase (2016-2021) to investigate the drivers of and barriers to routine vaccination in adults aged 50 and older globally. A thematic assessment identified three categories across 61 publications: sociodemographic, health-related, and attitudinal. The most common sociodemographic determinants (factors identified in studies; n = 47) associated with vaccination uptake were economic status, age, education, and household composition, which had mixed effects on vaccine uptake. For health-related determinants (n = 27), individuals with comorbidities and health care consumption were the most common factors, both increased vaccine uptake. The most common attitudinal factors (n = 42) were self-efficacy, provider or other's recommendations, and vaccine-preventable disease awareness; across studies, all attitude factors had a positive effect, unlike the sociodemographic and health status categories. Findings suggest that patient and provider awareness and education campaigns are effective ways to increase uptake of routine vaccinations in older adults.