Background <p>Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, and home-based pulmonary rehabilitation (HBPR) programs offer a promising non-pharmacological therapy. However, patient adherence to HBPR programs is far from satisfactory. This systematic review aims to synthesize existing evidence on the barriers and facilitators influencing adherence to HBPR programs in COPD patients from the perspective of healthcare professionals, family caregivers, and patients.</p> Methods <p>A systematic review of quantitative, qualitative, and mixed-methods studies was undertaken using PubMed, Web of Science, Embase, Cochrane Library, and CINAHL. Two independent researchers applied the eligibility criteria and extracted the data onto a predetermined form. The Mixed Methods Appraisal Tool was applied to assess the methodological quality of eligible studies. The data were synthesized using a convergent integration approach and categorized according to the COM-B dimensions (i.e., capability, opportunity, and motivation) and participant types (i.e., healthcare professionals, family caregivers, and COPD patients).</p> Results <p>A total of 21 studies (9 qualitative, 8 quantitative, and 4 mixed-methods studies) were included, involving 1444 COPD patients, 153 healthcare professionals, and 17 family caregivers. A total of 76 barriers and 73 facilitators were identified and mapped onto the COM-B model. For COPD patients, the most frequent facilitators were self-management skills (capability), perceived support from healthcare professionals (opportunity), and positive attitudes (motivation). The most frequent barriers were poor use of technical equipment (capability), lack of resources (opportunity), and psychological tensions (motivation). For healthcare professionals, professional competence (capability) and attitudes towards HBPR programs (motivation) were the most common barriers and facilitators, respectively. In the opportunity dimension, resources and collaboration with healthcare professionals were the most common barriers and facilitators, respectively. There was no consistent barrier/facilitator category for family caregivers.</p> Conclusion <p>The introduction of HBPR programs for COPD patients necessitates a tailored approach that considers the patient’s capability, opportunity, and motivation to improve adherence to HBPR programs. The active engagement of stakeholders is pivotal in guiding the evolution of interventions and ensuring effective clinical practice.</p>