There is an imbalance between demand for and availability of stem cell donors worldwide. The purpose of this systematic review is to provide the first comprehensive understanding of facilitators and barriers influencing unrelated stem cell donation (USCD) in adults, through a data synthesis of qualitative and quantitative evidence. Identification of the facilitators and barriers associated with stem cell donation intention and behaviour is essential to inform the development of behaviour change interventions to meet the current demand. Four databases were searched (Embase, PsycINFO, MEDLINE and CINAHL) and the last search was in February 2021. The search was limited to studies written in English and published from 1980 to present. Screening, quality assessment, data extraction and data synthesis incorporating the COM-B model were undertaken in line with the Joanna Briggs Institute methodology for an integrated mixed-methods review. Fifty studies were included in the review, analysis and mapping produced four integrated findings. Donation-related knowledge was a facilitator and conversely, lack of knowledge was a barrier to donation related behaviours. Perceived convenience, positive social influences, religious beliefs and the accessibility of positive donation-related social norms promoted positive donation related behaviours. Altruism and sense of duty were the most commonly cited motives for donation related behaviours.Through mapping to the COM-B model, Communication/Marketing, and Service Provision are the primary policy categories that can be used to change donation related behaviours. Future interventions should focus on targeted education regarding unrelated stem cell donation and creating recruitment campaigns that emphasise the life-saving potential of donation.