Work-related stress (WRS) has been widely recognized as an emerging occupational health issue, resulting in negative ramifications to employees’ health due to the pressures of the contemporary workplace environment. Since the nurses working in ER deal with the imminent situations of life or death of their patients, they are forced to act rapidly without prior planning which significantly raises their stress levels, subsequently leading to injuries. Whilst there are numerous legislative standards and industry protocols in place to reduce WRS, the average cost of claims and injury incidence have only further increased. The aim of this article is to critically review the significance of WRS in the healthcare organization among ER nurses. Therefore, this article will provide insights on the economic burden related to WRS with focus on healthcare industry. The critical interplay of the manifestation of WRS as potential health hazards and their harmful effects on ER nurses will be discussed in-depth. Finally, the review will outline the best practices employed in minimizing WRS for further improvement.