The healthcare sector is essential for any country because it indirectly affects its economy. The productivity of land will increase if there is a healthy workforce, and it will enhance its economy, which will, in return, lead to the human welfare of the country. The present quantitative study has investigated the relationship between high-performance work systems (HPWS) on safety workarounds through the role of burnout as mediation, and explored coping strategies as a moderator between burnout and safety workarounds. These constructs play a vital role in efficiently managing different organizational activities to generate better productivity and employee performance, and educate employees about rules that can be used and adopted to ensure a healthy work-life. The data were collected from 550 nurses through a questionnaire in the healthcare sector of Lahore, Punjab (Pakistan). AMOS and SPSS were used to test the direct relationships between the constructs, and analyze the moderation of coping strategies and the mediation effect of burnout. The results have demonstrated the strong moderated mediation of coping strategies and burnout between existing HPWS and safety workarounds. The study of coping strategies would help managers and employees handle job stress and alleviate burnout in the healthcare sector through safety workarounds to increase effectiveness and efficiency.