Nepal, with a concentrated HIV epidemic and high burden of tuberculosis (TB) and malaria, was perceived to have immensely benefited from grants by the Global Fund to Fight AIDS, Tuberculosis and Malaria in addressing the three diseases, amounting to total approved funding of US$80 million. This paper looks at the interaction and integration of Global Fund-supported programmes and national health systems. A mixed method ‘case study’ approach based on the Systemic Rapid Assessment Toolkit (SYSRA) was used to systematically analyse across the main health systems functional domains. The Country Coordinating Mechanism has been credited with providing the stewardship in attracting additional resources and providing oversight. The involvement of civil society for delivering key HIV and malaria interventions targeting high-risk groups was perceived to be highly beneficial. TB and malaria services were found to be well integrated into the public health care delivery system, while HIV services targeting at-risk groups were often delivered using parallel structures. Political instability, absence of continuity in leadership and sub-optimal investments in health were together perceived to have led to fragmentation of financing and planning activities, especially in HIV the programme. The demand for timely programmatic and financial reporting for donor-supported programmes has contributed to the creation of parallel monitoring and evaluation structures, with missed opportunities for strengthening and utilizing the national health management information systems.