Background: Non-communicable diseases (NCDs) require multifaceted responses from healthcare systems that must complement sustainable healthcare programs. Objectives: This study aims to investigate the current state of sustainability of Non-Communicable Disease Prevention and Control Programs (NCP-PCP) and to identify related challenges in various intra- and inter-organizational domains. Methods: This mixed-methods study used a researcher-made sustainability assessment tool and qualitative interviews of 46 managers responsible for implementing NCP-PCP in Iran. Graneheim and Lundman's approach, as well as descriptive statistics, were utilized to analyze the data. The sustainability questionnaire comprised nine domains: environmental support, funding stability, partnerships, organizational capacity, program evaluation, program adaptation, communications, strategic planning, and law and governance. Results: The overall mean score for sustainability was 3.54 ± 0.86, with funding stability (2.79 ± 1.03) and program adaptation (4.24 ± 1.12) receiving the lowest and highest mean scores, respectively. Qualitative data revealed several challenges, including financial instability, lack of budget allocation for such programs, absence of specific mechanisms for program evaluation, inadequate resources, deficiencies in intersectoral cooperation, and failure to utilize hidden community capacities. Conclusions: It is crucial to maintain and strengthen the current state of program adaptation and program evaluation to ensure the sustainability of NCD-PCP. On the other hand, funding instability is a significant obstacle in prevention and control programs that can bring the entire program to a halt, regardless of its sustainability in other domains.