Background Work–family conflict is a type of interrole conflict that occurs as a result of incompatible role pressures from the work and family domains. Work role characteristics that are associated with work demands refer to pressures arising from excessive workload and time pressures. Literature suggests that work demands such as number of hours worked, workload, shift work are positively associated with work–family conflict, which, in turn is related to poor mental health and negative organizational attitudes. The role of social support has been an issue of debate in the literature. This study examined social support both as a moderator and a main effect in the relationship among work demands, work-to-family conflict, and satisfaction with job and life. Objectives This study examined the extent to which work demands (i.e., work overload, irregular work schedules, long hours of work, and overtime work) were related to work-to-family conflict as well as life and job satisfaction of nurses in Turkey. The role of supervisory support in the relationship among work demands, work-to-family conflict, and satisfaction with job and life was also investigated. Design and methods The sample was comprised of 243 participants: 106 academic nurses (43.6%) and 137 clinical nurses (56.4%). All of the respondents were female. The research instrument was a questionnaire comprising nine parts. The variables were measured under four categories: work demands, work support (i.e., supervisory support), work-to-family conflict and its outcomes (i.e., life and job satisfaction). Results The structural equation modeling results showed that work overload and irregular work schedules were the significant predictors of work-to-family conflict and that work-to-family conflict was associated with lower job and life satisfaction. Moderated multiple regression analyses showed that social support from the supervisor did not moderate the relationships among work demands, work-to-family conflict, and satisfaction with job and life. Exploratory analyses suggested that social support could be best conceptualized as the main effect directly influencing work-to-family conflict and job satisfaction. Conclusion Nurses’ psychological well-being and organizational attitudes could be enhanced by rearranging work conditions to reduce excessive workload and irregular work schedule. Also, leadership development programs should be implemented to increase the instrumental and emotional support of the supervisors.