The ability to adapt to night shift work varies greatly among individuals, but little is known about how personal traits and coping strategies interact to affect shift-work tolerance. This study aimed to identify how certain personal traits (e.g., flexibility, languidness, chronotype, and neuroticism) and behavioral and coping strategies influence shift-work tolerance. Additionally, it explored whether behavioral and coping strategies moderate the association between neuroticism and shift-work tolerance. In this cross-sectional study, nurses (N=297) working rotating shifts consisting of either three 8-h shifts or two 12-h shifts at two university hospitals and one training hospital in South Korea completed a survey on shift work. Data were analyzed using hierarchical multiple linear regression analysis. Nurses with personal traits of lower flexibility, higher languidness, evening-oriented chronotypes, and higher neuroticism had less shift-work tolerance. Engagement-coping decreased fatigue, whereas disengagement-coping increased insomnia. Among those with higher levels of neuroticism, disengagement-coping further reduced alertness, while engagement-coping aggravated insomnia. Addressing the complex interplay between personal traits and coping strategies is essential to enhance adaptations to shift work without adverse consequences.