The objective of this study is to examine the mediating role of enterprise resource planning (ERP) system adoption on the relationship between performance of medium enterprises (PMEs) and organizational culture (OC), communication process (CP), organizational structure (OS), information technology readiness (ITR), technological change (TC), government policy (GP), information access (IA) and technology infrastructure support (TIS). This study also includes the role of top management support (TMS) as a moderating variable on the relationship between ERP and PME. This study proposes a theoretical framework based on theories such as resource-based view, contingency theory and diffusion of innovation. The data were collected from medium-sized enterprise (ME) organizations operating in South Western Nigeria. A total of 658 questionnaires were distributed to selected MEs and only 355 were returned and used for the analysis. The empirical data were analyzed using the Partial Least Squares Structural Equation Modelling (PLS-SEM). The results showed that CP, ERP, GP, IA, ITR, OC, OS, TC, TIS and TMS have significant direct relationships with the ERP and PME while GP is not significantly linked to ERP adoption. Moreover, IA, ITR, OC, OS and TC have no significant relationship with PME while ERP system adoption mediates the relationship between the CP, OC, OS, TC and TIS with PME. The findings showed that the presence of CP, OC, OS, TC and TIS will influence the PMEs in the adoption of ERP and confirmed that TMS plays an important role in moderating the relationship between ERP and PME. The findings provide important insights to CEO, managers, policymakers and researchers to help them understand the importance of using the ERP system to enhance the performance of medium-sized enterprise (PMSE) organizations. Limitation of the study is based on MEs only. In this light, future research can focus on the evolution of not only small enterprises but also large firms.