Background <p>The use of computerised clinical decision support systems (CDSSs) holds considerable potential in enhancing healthcare delivery by improving patient safety, practitioner performance, and patient outcomes. However, despite the numerous reported advantages of CDSSs, their adoption remains restricted, thereby compromising the full realisation of their potential. To enable a profound evaluation and successful implementation of these systems, it is imperative to identify the reasons for their limited uptake. The objective of this study is to provide a comprehensive overview of the barriers and facilitators to the implementation and adoption of decision support systems across healthcare settings.</p> Methods <p>This study was reported in accordance with the Preferred Reporting Items for Overviews of Reviews (PRIOR) statement. A systematic search was conducted in the databases PubMed, IEEE Xplore, Scopus, and Web of Science from inception to 15 October 2024, targeting at review articles of primary studies focusing on the identification and reporting of barriers and facilitators to the implementation and adoption of CDSSs across healthcare settings. The risk of bias of the included reviews was assessed with the Risk of Bias in Systematic Reviews (ROBIS) tool, and the primary study overlap was calculated using the corrected covered area method. All data on barriers and facilitators to the implementation and adoption of CDSSs were extracted from the included reviews, synthesised through a mapping of identical factors, and ranked according to their frequency of occurrence.</p> Results <p>Of the 1640 records retrieved through database searches, 30 reviews were included in this overview, which summarised the findings of 721 unique primary studies. A total of 101 distinct factors influencing the implementation and adoption of CDSSs were identified and could be categorised into the overarching categories of human, technology-related, and contextual factors. The following six factors were reported most frequently: usability, usefulness/perceived benefits, organisational readiness, training, trust, and workflow integration.</p> Conclusions <p>The findings of this study highlight the diversity of factors that influence a successful implementation of CDSSs and emphasise the need for their comprehensive evaluation that goes beyond the assessment of general performance aspects but takes into account human and contextual factors.</p> Systematic review registration <p>PROSPERO CRD42024507614.</p>