Background: The present research extended previous research by broadening the dimensions of personality traits, and focusing on burnout and psychological well-being among staff working with people with intellectual disabilities and challenging behaviour. Methods: This is a cross-sectional survey in which 103 staff completed questionnaires measuring clients' challenging behaviour according to staff perception, as well as staff burnout, psychological well-being and personality traits. Results: Regression analyses showed that staff perception of challenging behaviour predicted burnout. Controlling for challenging behaviour, three personality traits (neuroticism, extraversion and conscientiousness) predicted burnout and psychological well-being. Conclusions: Personality traits can affect the degree of burnout and poor psychological well-being that staff may experience. Staff should be informed about the role that their personality traits can play in their well-being. Training programmes for staff should incorporate the complex relationship between personality traits and well-being. Further studies should aim at identifying other personality traits that could increase or decrease resilience of staff working in this area.