The aim of this systematic mixed-studies review is to summarise barriers/facilitators to adherence to and/or consumption of oral nutritional supplements (ONS) among patients with disease-related malnutrition. In March 2022, the Cochrane CENTRAL, PUBMED, PsycINFO (Ovid) and CINAHL were searched for articles with various study designs, published since 2000. Articles were identified on the basis of 'population' (patients ≥18 years with malnutrition/at nutritional risk), 'intervention' (ONS with ≥2 macronutrients and micronutrients), 'comparison' (any comparator/no comparator) and 'outcome' (factors affecting adherence or consumption) criteria. A sequential exploratory synthesis was conducted: first, a thematic synthesis was performed identifying barriers/facilitators; and second, the randomised controlled trials (RCTs) were used to support these findings. The five WHO dimensions of adherence guided the analysis. Study inclusion, data extraction, analysis and risk-of-bias assessment (MMAT 2018) were carried out independently by two researchers. From 21 835 screened articles, 171 were included with 42% RCTs and 20% qualitative studies. The two major populations were patients with malignancies (34%) and older adults (35%). In total, fifty-nine barriers/facilitators were identified. Patients' health status, motivation, product tolerance and satisfaction as well as well-functioning healthcare routines and support were factors impacting ONS consumption. Few barriers/facilitators (n = 13) were investigated in RCTs. Two of those were serving a small ONS volume and integrating ONS into ward routines. Given the complexity of ONS adherence, non-adherence to ONS should be addressed using a holistic approach. More studies are needed to investigate the effect of different approaches to increase adherence to ONS.