ERP systems are integrated information systems (IIS) popularly used among tertiary institutions in the globe. ERP has attained familiarization in certain parts of the globe due to its huge acquisition in tertiary institutions. Notwithstanding the rising acquisition, choice and execution of ERPs in higher education, there remains a scarcity in literature about their performance, especially in the developing world. It is, therefore, important to further examine whether these ERPs fulfill their anticipated benefits. This paper aims to evaluate the effectiveness of KNUST’s enterprise system (comprising ARMIS, Panacea, and Synergy Systems) in HEIs through a system integrative framework. A combined-method research approach was employed, collecting data from a sample of 60 respondents for both quantitative and qualitative investigation. The data were examined through partial least squares structural equation modeling (PLS-SEM) and inductive thematic analysis. The study’s results revealed that the customer/stakeholder perspective, learning–growth perspective, financial perspective, and system quality perspective significantly influence and positively relate to the effectiveness of KNUST’s enterprise system evaluation in Ghanaian higher education. Internal business process, according to the findings, was the only perspective that had no significant impact on the performance of KNUST enterprise system in the Ghanaian higher education. Works on ERPs assessments, readiness, and implementations are scarce in developing world, particularly in the Ghanaian context. This study has successfully assessed the KNUST enterprise system, demonstrating its effectiveness through the research model deployed.