BACKGROUND: The Malaria Vaccine Implementation Program, coordinated by the World Health Organization, intended to initiate the roll-out of the RTS, S/AS01 malaria vaccine in 3 sub-Saharan African countries in 2018. With sub-optimal implementation, the effectiveness of this vaccine in routine clinical use could be significantly lower than its measured efficacy in randomized trials. This study had as objectives to systematically review and summarize published studies addressing the challenges faced during the implementation phase of malaria vaccination programs and randomized trials conducted in sub-Saharan Africa. The review also sought to report proposed solutions to the challenges identified. METHOD: This was a systematic review of studies published between 1947 and 2017. Medline, Embase and the Cochrane library databases were searched. Of the 365 studies retrieved, 8 eligible studies reported on challenges of implementing a malaria vaccine in sub-Saharan Africa and possible solutions to these challenges. Data were abstracted from the eligible studies and a qualitative synthesis was done. RESULTS: The 8 studies included in the review had a total of 6189 participants and used a variety of methodologies (3 qualitative, 1 quantitative, 3 mixed method studies and 1 clinical trial review). There was an overall positive acceptance towards the new malaria vaccine (n = 6/8 studies), with a mean acceptance rate of 86.1% (95% CI: 62.0-110.2, n = 2). The main challenges to vaccine receptivity were: inadequate community engagement due to lack of information about the vaccine (n = 6), fear of the vaccine's side effects (n = 5), inefficient delivery of vaccination services to children (n = 4), and sub-optimal quality of the health services (n = 3). Main themes identified from the proposed solutions consisted of the following: using dynamic communication models and trusted sources for delivering vaccine-related health information to the communities (n = 6), community engagement at both national and district level (n = 6), implementing the new vaccine services alongside the existing health services already delivered (n = 6). CONCLUSION/RECOMMENDATIONS: Effective implementation of the malaria vaccine program requires careful consideration of the socio-cultural context of each community. The RTS, S/AS01 malaria vaccine acceptance and uptake may be significantly enhanced if caregivers' perceptions about vaccines and their importance are adequately fine-tuned. In order to achieve these, community participation and the provision of adequate information in an acceptable form via reliable communication channels seem to be imperative.