Kangaroo mother care (KMC) is an evidence-based approach to reducing mortality and morbidity in preterm infants. Although KMC is a key intervention package in newborn health initiatives, there is limited systematic information available on the barriers to KMC practice that mothers and other stakeholders face while practicing KMC. This systematic review sought to identify the most frequently reported barriers to KMC practice for mothers, fathers, and health practitioners, as well as the most frequently reported enablers to practice for mothers. We searched nine electronic databases and relevant reference lists for publications reporting barriers or enablers to KMC practice. We identified 1,264 unique publications, of which 103 were included based on pre-specified criteria. Publications were scanned for all barriers / enablers. Each publication was also categorized based on its approach to identification of barriers / enablers, and more weight was assigned to publications which had systematically sought to understand factors influencing KMC practice. Four of the top five ranked barriers to KMC practice for mothers were resource-related: “Issues with the facility environment / resources,” “negative impressions of staff attitudes or interactions with staff,” “lack of help with KMC practice or other obligations,” and “low awareness of KMC / infant health.” Considering only publications from low- and middle-income countries, “pain / fatigue” was ranked higher than when considering all publications. Top enablers to practice were included “mother-infant attachment” and “support from family, friends, and other mentors.” Our findings suggest that mother can understand and enjoy KMC, and it has benefits for mothers, infants, and families. However, continuous KMC may be physically and emotionally difficult, and often requires support from family members, health practitioners, or other mothers. These findings can serve as a starting point for researchers and program implementers looking to improve KMC programs.