PurposeMany organizations failed to generate profits after investing considerable money and time in Enterprise Resource Planning (ERP) systems. This study, therefore, sought to identify the challenges encountered by pharmaceutical firms during the post-implementation of ERP systems.Design/methodology/approachA case-based study followed by general survey-based research was carried out in pharmaceutical firms to determine the critical post-implementation challenges of ERP systems. DANP (DEMATEL-based ANP) and Wilcoxon Signed Rank test were used to find the causal/critical challenges and rank them.FindingsAfter analyzing a pharmaceutical case company and conducting a general survey among pharmaceutical companies, statistical analysis was performed to identify the most significant challenges, namely, “Inefficient troubleshooting mechanism”, “Lack of training during post-implementation stage” and “Difficulty in identifying invalid data when entered into the ERP system”. Furthermore, organization-wide challenges are considered to be the most important.Practical implicationsThe paper identifies the challenges faced during the post-implementation phase of ERP systems. This work brings out the issues with ERP systems' performance after their implementation, which is related to the quality of the ERP systems. This work will support the risk identification and mitigation during ERP implementation to eradicate the problems after its implementation. This work may trigger the ERP system developers to improve its features and performance for better manufacturing and supply chain management system in pharmaceutical firms.Originality/valueThis study is uniquely conducted in pharmaceutical firms to study the benefits and challenges of adopted ERP systems. A pilot case study served as the foundation for the generalizability of other pharmaceutical firms' findings through a non-parametric test.