The government of Ethiopia has been acknowledging that the implementation of integrated functional adult education (IFAE) program is the responsibility of different sectors. However, reports and studies indicated that the collaboration of sectors is low. Yet, the factors that impede and enhance the collaboration were not indicated. Therefore, the purpose of this study was to assess the major factors that enhance and deter inter-sectoral collaboration (ISC) in the implementation of IFAE program in South Gondar Zone. To achieve this purpose, the study used a convergent mixed research design. The necessary data were collected from 52 Adult Education Board (AEB) members, 36 Adult Education Technical Committee (AETC) members and nine IFAE program facilitators through questionnaire and interview. Data was also collected from official documents through document review. The data was analyzed using thematic analysis approach by comparing results obtained from qualitative and quantitative analysis without converting either one of to the other one. The finding a indicated that the overall participation of sectors in the collaboration was very low and alarming. Compared to other sectors, the education sector contributes more to the implementation of IFAE program. The study has shown that, among others, low political commitment; lack of responsibility among collaborative sectors; absence of independent sector that facilitate the IFAE program; lack of clear implementation guideline; absence of holistic and harmonized plan; low community engagement; lack of discussion among partners; and lack of financial and human resources were barriers for ISC. The finding also indicated that providing strong political support from government; active participation of the community in the collaboration; guiding the collaboration with an inclusive and harmonized plan; developing clear implementation guideline; conducting regular discussion among sectors; and providing adequate financial and human resources are strategies to enhance ISC in the implementation of IFAE program, among others. The study has shown that factors that deter and enhance ISC are interrelated, and most of the factors are one way or the other influenced by political commitment of the government from Federal to Kebele levels. Therefore, much emphasis should be given for political advocacy for the program. A serious political directive must be given for each collaborative sector leaders so that they give attention for the collaboration. A clear implementation guideline, which provides clear responsibilities and accountabilities for sectors, should be developed. Moreover, policy makers should develop a strong policy, which can be legitimized in declarations. A mass awareness about the relevance of the program should be created for the community and influential community members should be involved in the collaboration.