Objectives: The aim of this systematic review is to compare the effectiveness of eHealth self-management interventions on pain intensity between oncological and musculoskeletal populations and to examine barriers and facilitators of the use of eHealth self-management tools., Content: In March 2021, a systematic search of the literature was conducted using the databases PubMed and Web of Science. Studies that investigated the effect of eHealth self-management interventions on pain intensity in an oncological and/or a musculoskeletal population were included., Summary: No study was found with a direct comparison of the two populations. Of the ten included studies, only one (musculoskeletal) found a significant interaction effect in favor of the eHealth program and three (musculoskeletal and breast cancer) showed a significant time-effect of the eHealth intervention. In both populations user-friendliness of the tool was considered as a facilitator, the length of the program and the lack of an in-person session as barrier. Due to the absence of a direct comparison, no conclusion can be made on how the effectiveness differs between both populations., Outlook: Further research should incorporate patient-experienced barriers and facilitators and there is a high need of studies making the direct comparison of the effect of an eHealth self-management intervention on pain intensity in an oncological vs. a MSK population., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)