The growing attention paid to employee well-being in the healthcare system, along with the reinforcement of factors that drive change in the work environment, provides a strong foundation for studying the relationship between work design and its related outcomes. The aim of this study was to examine the relationship between the elements of work design and the overall well-being of healthcare professionals, particularly the differences across multiple groups of various genders and age brackets. A cross-sectional study design was employed, and a convenience sampling method was used. The study participants were healthcare professionals, and a total of 427 valid surveys were collected. The partial least squares structural equation modeling (PLS-SEM) approach was deployed to test the relationship between the determinants of work design and the perceived well-being of healthcare professionals. The results indicate a strong positive relationship between the social characteristics of work and overall well-being, as well as a positive contribution of the work context to the perceived well-being of healthcare professionals. The findings validated that knowledge characteristics had no beneficial impacts on overall well-being; nor did the task characteristics of work design. Although the mentioned associations failed to demonstrate statistical significance, the results nonetheless have significant practical consequences that are comparable to those of the relationships that demonstrated statistical significance.