Integration of services for patients with more than one diagnosed condition has intuitive appeal but it has been argued that the empirical evidence to support it is limited. We report the findings of a systematic review that sought to identify health system factors, extrinsic to the integration process, which either facilitated or hindered the integration of services for two common disorders, HIV and chronic non-communicable diseases. Findings were initially extracted and organized around a health system framework, followed by a thematic cross-cutting analysis and validation steps. Of the 150 articles included, 67% (n = 102) were from high-income countries. The articles explored integration with services for one or several chronic disorders, the most studied being alcohol or substance use disorders (47.7%), and mental health issues (29.5%). Four cross-cutting themes related to the health system were identified. The first and most common theme was the requirement for effective collaboration and coordination: formal and informal productive relationships throughout the system between providers and within teams, and between staff and patients. The second was the need for adequate and appropriately skilled and incentivized health workers-with the right expertise, training and operational support for the programme. The third was the need for supportive institutional structures and dedicated resources. The fourth was leadership in terms of political will, effective managerial oversight and organizational culture, indicating that actual implementation is as important as programme design. A fifth theme, outside the health system, but underpinning all aspects of the system operation, was that placing the patient at the centre of service delivery and responding holistically to their diverse needs. This was an important facilitator of integration. These findings confirm that integration processes in service delivery depend substantially for their success on characteristics of the health systems in which they are embedded.