This study examined the impact of team-based working, team structure, and job design on employee well-being (in term of job satisfaction and work stress) in staff working in healthcare organizations in Hong Kong. Cross-cultural differences in the impact of job design, team structure, and employee well-being outcomes between United Kingdom and Hong Kong were also investigated. A group of 197 staff from two Hong Kong hospitals were compared to a sample of 270 UK staff working in National Health Service organizations in the UK. Results showed that team structure and job design were significantly associated with greater employee satisfaction and lower stress for Hong Kong healthcare staff. Culture was also found to moderate the impact of team structure and job design on employee well-being. The findings suggest that although team structure and job design contribute to employee well-being, they have differential impacts across cultures. This provides insights to policy planning on building team-based organizations in the healthcare sector involving multinational collaboration.