Purpose: The purpose of this research is to investigate the interrelationships among Knowledge Management (KM), Information Systems (IS), and Employees' Empowerment (EE) on Employees' Performance (EP). Design: Accordingly, a structural model is developed that delineates the interactions among these constructs and explores the mediating effect of employees' empowerment on the relationship between KM, IS and employees' performance. A questionnaire-based survey was designed to test the aforementioned model based on dataset of 287 employees' Pharmaceutical industries in Jordan. Results: The model and posited hypotheses were tested using structural equation modeling analysis. The results indicated that KM and IS positively and significantly affect EE, in which the latter impact EP as well. However, neither KM nor IS proved to be positively related to EP. Additionally, EE positively and significantly mediated the relationship between KM and EP; besides the relationship between IS and EP. Originality: This is one of the few studies which investigate the interrelationships among Knowledge Management (KM), Information Systems (IS), and Employees' Empowerment (EE) on Employees' Performance (EP), and the first to test the model on companies in the pharmaceutical industries in Jordan.