Chronic disease is well recognized as a significant health challenge in developed and many emerging economies. A key element in health system change is the role of leadership, management and organizational culture. The study aims to examine how leadership characteristics interact with management and influence the implementation of chronic disease management programs in Nepal. An interview was done with 12 key informants from various district health offices in Province 1 of Nepal. The participants were district health officers and senior managers in charge of chronic disease management programs. The semi-structured interviews were transcribed into Nepali and then translated into English. Leaders at the district level are constantly challenged in addressing the lack of human, material and technical resources in implementing chronic disease programs. This shortage impacts the decision-making and handling of social and professional workplace relationships by the leaders. Leaders from the district described the necessity of building strategic alliances with stakeholders from across the public sector and non-governmental organizations. These alliances were crucial to resource mobilization, garnering material support, expanding healthcare access and community outreach, and compensating for capacity constraints within the districts to address the issues in the implementation of NCD programs at the district level. Participants framed their leadership as a moral drive to change and some leadership styles used are democratic leadership, servant leadership, and collaborative leadership, which is leveraged flexibly depending on the demands of the moment or the task at hand. The study provided a critical, preliminary understanding of leadership and challenges in healthcare. We found that there is a demand for healthcare leadership development, which will undoubtedly improve the health systems managerial, administrative and teamwork capacities at a micro-level in strengthening healthcare and improving health outcomes.