The primary goal of the present study is to inspect the plausible job-related (i.e., challenge stressors and role blurring) and individual factors (i.e., fatigue and insomnia) that potentially lead to work-related cognitive failures among healthcare staff. Through the judgmental sampling technique, data was collected from healthcare personnel in Iran. The results revealed that challenge stressors in the form of time pressure, job responsibility, and work overload are significantly related to role blurring. Moreover, role blurring increases fatigue and insomnia among medical staff, and both insomnia and fatigue cause workplace cognitive failure. The results also confirm the mediation effect of role blurring in the association between challenge stressors, insomnia, and fatigue. According to the results, insomnia and fatigue similarly mediate the role blurring on workplace cognitive failure association. Theoretical implications, useful suggestions for practitioners, and prospective research avenues are debated in the study.