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The evolution and contemporary challenges of health research (HR) in Madagascar are poorly documented. We aim to gain insights on the factors that shape Madagascar's National Health Research System (NHRS) to better understand their influence. We conducted a qualitative case study, which included a documentary review and semi-structured interviews with 38 key informants. We carried out a thematic analysis and used the WHO/AFRO NHRS Barometer to structure the presentation of the results. There is no legislative framework to support HR activities and institutions. There is, however, a policy document outlining national priorities for HS. Human resources for HR are insufficient, due to challenges in training and retaining researchers. International collaboration is almost the only source of HR funding. Collaborations contribute to developing human and institutional capacity, but they are not always aligned with research carried out locally and the country's priority health needs. Incomplete efforts to improve regulation and low public investment in research training and research implementation reflect an insufficient commitment to HR by the government. Negotiating equitable international partnerships, the availability of public funding, and aligning HR with national health priorities would constitute a solid basis for the development of the NHRS in Madagascar., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêt., (Copyright: Joëlle Laure Sobngwi-Tambekou et al.)