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Background: Many countries' health systems are implementing reforms to improve the functioning and performance of the Health Management Information System (HMIS) to facilitate evidence-based decisions for delivery of accessible and quality health services. However, in some countries such efforts and initiatives have led to a complex HMIS ecosystem characterized by multiple and fragmented sub-systems. We undertook an in-depth analysis of the HMIS ecosystem in Tanzania to inform the ongoing initiatives, by understanding the relationship and power differences among stakeholders, as well as drivers and barriers to HMIS investment and strengthening. Methodology: This was a qualitative research method incorporating data collection through document review and key informant interviews guided by political economy analytical framework. A total of 17 key informant interviews were conducted between April and May 2022. A thematic content analysis was used during data analysis. Results: Good relationship between the government and stakeholders dealing/supporting HMIS ecosystem was noted as there are technical working groups which brings stakeholders together to discuss and harmonize HMIS activities. The 'need for the data' has been the driving force toward investment in the HMIS ecosystem. The analysis showed that the government is the main stakeholder within the HMIS ecosystem and responsible for identifying the needs for improvement and has the power to approve or reject systems which are not in line with the government priority as stipulated with the HMIS investment roadmap/strategy. Moreover, partners with long relationship are powerful in influencing HMIS investment decision-making compared to those who are recently coming to support. It was further noted shortage of staff with technical competence, inadequate financial resources, and the development of fact that some of the existing systems have not been developed to their full capacity and have hindered the whole systems' integration and interoperability exercise of ensuring integration and interoperability of the systems. Conclusion: A need-based assessment of staff capacity at the sub-national level is equally important to identify available capabilities and the knowledge gap to strengthen the HMIS ecosystem. Strong coordination of the ideas and resources intended to strengthen the HMIS ecosystem would help to reduce fragmentation. In addition, there is a need to mobilize resources within and outside the country to facilitate the integration and interoperability process smoothly. [ABSTRACT FROM AUTHOR]