The factors affecting nursing job satisfaction and burnout have been widely studied, but the research results vary in nations with different cultures and organization schemes. The healthcare system of Macao is unique, which tends to be a combination of that of Chinese and Portuguese. This study aimed to assess the factors influencing job satisfaction and burnout and to investigate their associations with demographic characteristics. This descriptive cross-sectional study was conducted among 345 randomly selected nurses registered with the Health Bureau of Macao Special Administrative Region who agreed to participate in this study voluntarily. This study employed two questionnaires using eight subscales (28 items) and five subscales (49 items) to describe job satisfaction and burnout, respectively. The demographic variables of age, highest education level, monthly income, type of working organization, and role were associated with job satisfaction. Whereas marital status was the only demographic variable associated with burnout. Professional development opportunities and childcare support were the main reasons for job dissatisfaction and coping strategies was the major issue for burnout. No significant correlation was found between job satisfaction and burnout. Health organizations may provide solutions focusing on these factors to enhance the job satisfaction of nurses and reduce burnout.