Introduction: Adults aged ≥65 years contribute a large proportion of influenza-related hospitalizations and deaths due to increased risk of complications, which result in high medical costs and reduced health-related quality of life (HRQoL). Although seasonal influenza vaccines are recommended for older adults, the effectiveness of current vaccines is dependent on several factors including strain matching and recipient demographic factors. Objective: This systemic literature review aimed to explore the economic and humanistic burden of influenza in adults aged ≥65 years. Methods: An electronic database search was conducted to identify studies assessing the economic and humanistic burden of influenza, including influenza symptoms that impact the HRQoL and patient related outcomes in adults aged ≥65 years. Studies were to be published in English and conducted in Germany, France, Spain, and Italy, United Kingdom, United States, Canada, China, Japan, Brazil, Saudi Arabia, and South Africa. Results: Twenty-five studies reported on the economic and humanistic burden of influenza in adults aged ≥65 years. Higher direct costs were reported for people at increased-risk of influenza-related complications compared to those at low-risk. Lower influenza-related total costs were found in those vaccinated with adjuvanted inactivated trivalent influenza vaccine (aTIV) compared to high-dose trivalent influenza vaccine (TIV-HD). Older age was associated with an increased occurrence and longer duration of certain influenza symptoms. Despite the limited data identified for, results show that influenza exerts a high humanistic and economic burden. in older adults. Further research is required to confirm findings and to identify the unmet needs of current vaccines.