This paper examines the drivers of job satisfaction across four cultural regions—Asia, Europe, North America, and Latin America. Using Hofstede’s theory, determinants were used to predict job satisfaction for each region and then compared to determine significant differences. Data was collected from a proprietary industry survey on employee work attitudes. The sample consisted of over 70,000 employees from 4 large multinational organizations. Data was analyzed using regression analysis and comparison testing across models. There are significant relationships between job characteristics and job satisfaction across all regions of the world, with a sense of achievement universally the most important driver. Although job characteristics impact job satisfaction across all regions, there are significant differences in the relative importance of job characteristics on job satisfaction, consistent with Hofstede’s cultural dimensions. The findings have implications for tailoring human resource management practices across locations within multinationals.This research is believed to be the first cross-cultural study of the job determinants affecting job satisfaction using multiple organizations and industries.