A systematic literature review was conducted to summarize the existing evidence on presumed determinants of heart failure (HF) medication adherence. The aim was to assess the evidence and provide directions for future medication adherence interventions for HF patients. Based on a search in relevant databases and a quality assessment, eleven articles were included in the review. A best evidence synthesis was used to combine the results of presumed determinants that were found more than once in the literature. Results were classified according the World Health Organization’s (WHO) multidimensional adherence model. Results demonstrated a relationship between having been institutionalized in the past (including hospitalizations and nursing home visits) and higher adherence levels. This finding is related to the healthcare system dimension of the WHO model. The presumed determinants related to the other dimensions, such as social and economic factors, condition-related, therapy-related, and patient-related factors of the multidimensional adherence model all had inconsistent evidence. However, there was also an indication that patients’ educational level and the number of healthcare professionals they have visited are not related to higher adherence levels. Based on the current review, HF patients who have been institutionalized in the past are more adherent to HF medication. Many other presumed determinants were investigated, but displayed inconsistent evidence. Due to the lack of evidence, it was not possible to make recommendations for future interventions.