In the pursuit of well-being at work, work stress is always an inescapable challenge. However, existing research shows that the relationships between work stress and employee outcomes are inconsistent, which indicates that the concept of work stress needs further investigation. Moreover, Zhong-Yong serves as a cognitive strategy to coping with stress as well as being a pivotal life wisdom and practical rationality. Using a questionnaire survey, this study explores the relationship between work stress, employee well-being, and Zhong-Yong beliefs. The work stress was classified into challenge- and hindrance-related stress while emotional exhaustion and job satisfaction were used as well-being indicators. Using a sample of 394 employees from private enterprises in Taiwan as subjects, the results show that (1) hindrance-related stress is destructive to employee well-being; (2) challenge-related stress is positively associated with emotional exhaustion but has no significant relation with job satisfaction; (3) Zhong-Yong beliefs mitigate the harm from hindrance-related stress on employee well-being; and (4) Zhong-Yong beliefs weaken the negative effects of challenge-related stress on emotional exhaustion, and transform challenge-related stress into eustress for job satisfaction.