The world of work has changed at an unprecedented pace in the past three decades. Social epidemiology examines the patterns of social determinants of health, and it provides powerful systems approaches to population health. In the context of globalization, rapid technological advances, economic openness, and global interconnectedness have provided opportunities for economic growth but have also inevitably led to fierce competition, altered the nature of work, and exposed workers to new health risks. This chapter presents the health challenges including health inequalities in relation to globalization and technological change, and it then uses a multilevel framework to explain how changes at the international and organizational levels driven by globalization can impact workers’ health. This chapter takes a social epidemiological approach to address the complex interaction of social, economic, and structural determinants on health. Finally, a e study is presented to demonstrate how a quantitative systematic review can be developed to inform social epidemiological research and workplace policies to improve employee health.