Employees and employers were thrown into uncertainty and chaos during the period of the COVID-19 pandemic, where they had no clear idea of exactly what they should do. Human resource managers operated in crisis mode since the beginning of the pandemic, that is, from 2020 to the first half of 2021. In this period, human resource managers sorted out the possibilities and probabilities on how employees could work from home and formulated strategies for providing them with extra mental and physical care, and they worked harder than ever on corporate-level initiatives to maintain the operations of their companies. The function of Human Resource (HR) has fundamentally changed as businesses have adapted to a new normal and the dust continues to settle. Throughout the pandemic, non-clinical organizations faced uncertain challenges, strategies, and had to make unique decisions regarding human resource management. There have been a variety of detrimental consequences associated with the COVID-19 pandemic, including economic shocks, global health crisis, changes in social behaviors, and challenges for businesses in sustaining their operations. The role of information systems in the management of human resources during the COVID-19 pandemic has been studied in this research. After gathering 400 records from credible publications, duplicates were removed, inclusion and exclusion criteria were used, and 130 papers were finally included in this research. By analyzing the selected papers, it was found in this study that organizations need to be flexible, improve their internal efficiency, acquire talent, and implement innovative changes based on organizational needs in order to ensure smooth business operations. It is possible to improve employees’ mental health, satisfaction, productivity, motivation, and workplace health and safety by implementing appropriate human resource management strategies and innovative information systems and IT tools. A conceptual model that establishes relationships between variables is also presented as an outcome of this research.