The advancement of theory and research on macrosocial determinants of health has been identified as a promising path for future social epidemiology. In this commentary, we outline how macrosocial epidemiology can advance in two critical ways: (1) engaging scientific realism, and (2) incorporating social conflict. The first describes how scientific realism can be effectively applied within macrosocial epidemiology to identify the specific contexts in which social mechanisms are triggered, which in turn, generate health outcomes. Engaging scientific realism fosters a deeper understanding on how and why macrosocial factors, processes, and institutions are causally linked to population health. The second makes the case to incorporate a social conflict paradigm into macrosocial epidemiology. Thinking in terms of social conflict allows us to view social structures as inequality-generating mechanisms, and re-orients our public health efforts toward social change, including for example, taking action on unequal political, economic, and cultural relations.