This study was conducted to investigate the relationship between Management Information Systems (MIS) and the loan performance of selected Microfinance Institutions (MFIs) in Mukono District. A cross-sectional survey design was employed, and data were collected using a semi-structured questionnaire from a sample of 85 respondents, comprising managers, loan officers, and credit staff from purposively selected MFIs. The data were analyzed using both descriptive and inferential statistics, with Pearson’s Correlation and Linear Regression used to test the hypothesis. The results of the descriptive statistics revealed that the usage of MIS was positively perceived by respondents as a significant contributor to loan performance. The mean scores for all statements regarding MIS efficacy ranged from 4.07 to 4.21, indicating strong agreement that MIS facilitates efficient loan tracking, enables timely reporting, and enhances data-driven decision-making. The standard deviations, ranging from 0.91 to 0.97, suggested a moderate consensus among the participants. These findings demonstrated that digital systems were widely viewed as critical for managing loan portfolios and mitigating default risks. The inferential analysis further established a statistically significant positive relationship between MIS implementation and key loan performance metrics. The study concluded that Management Information Systems serve as a strategic asset, rather than a mere operational tool, significantly enhancing loan performance in Microfinance Institutions within Mukono District. The findings were consistent with the Resource-Based View (RBV) Theory, positing that a well-integrated MIS constitutes a valuable, rare, and inimitable resource that grants MFIs a competitive advantage through superior loan portfolio management. The study therefore recommended that Microfinance Institutions should prioritize sustained investment in robust and integrated MIS infrastructure to fortify their operational capabilities. Furthermore, it was recommended that management should ensure comprehensive training for staff on digital monitoring tools and foster a culture of data-driven decision-making across all departments to sustain and enhance loan recovery rates and overall financial health.