Abstract Background Vaccination against influenza is considered the most important public health intervention to prevent unnecessary hospitalizations and premature deaths related to influenza in the elderly, though there are significant inequities among global influenza vaccine resources, capacities, and policies. The objective of this study was to assess the social determinants of health preventing adults ≥65 years old from accessing and accepting seasonal influenza vaccination. Methods A systematic search was performed in January 2011 using MEDLINE, ISI – Web of Science, PsycINFO, and CINAHL (1980–2011). Reference lists of articles were also examined. Selection criteria included qualitative and quantitative studies written in English that examined social determinants of and barriers against seasonal influenza vaccination among adults≥65 years. Two authors performed the quality assessment and data extraction. Thematic analysis was the main approach for joint synthesis, using identification and juxtaposition of themes associated with vaccination. Results Overall, 58 studies were analyzed. Structural social determinants such as age, gender, marital status, education, ethnicity, socio-economic status, social and cultural values, as well as intermediary determinants including housing-place of residence, behavioral beliefs, social influences, previous vaccine experiences, perceived susceptibility, sources of information, and perceived health status influenced seasonal influenza vaccination. Healthcare system related factors including accessibility, affordability, knowledge and attitudes about vaccination, and physicians’ advice were also important determinants of vaccination. Conclusions Our results demonstrate that the ability of adults ≥65 years to receive seasonal influenza vaccine is influenced by structural, intermediate, and healthcare-related social determinants which have an impact at the health system, provider, and individual levels.