This study examined the effects of exposure to resident aggression, self-efficacy, neuroticism, and attitudes toward dementia on burnout among direct care workers (DCWs) in nursing homes. A convenience sample of 800 DCWs from 70 randomly selected nursing homes in Hong Kong were recruited and individually interviewed. DCWs reported past-month experiences of resident aggression, levels of burnout, self-efficacy, neuroticism, attitudes toward dementia, and other personal and facility characteristics. Hierarchical multiple regression analysis revealed that, while physical environment of the facilities, and demographic background and self-efficacy of DCWs were not significant contributing factors, DCWs’ exposure to resident aggression, insufficient experience and training in dementia care, negative attitudes toward dementia, and neurotic personality were associated with higher levels of staff burnout. Findings point to the importance of mitigating resident aggression and adequately screen and train staff to optimize their empathy and competence in minimizing the risk of burnout.