To prepare for the health risks facing our society, the French Institute for Public Health Surveillance (InVS) has adopted a forward-looking approach that will take into account short-, medium-, and long-term developments, while regularly adjusting and reorienting the scenarios developed based on an analysis of current or recent changes in the social and economic environment and the population’s health status. The initiative was carried out internally in 2014. Five macro-scenarios were developed: "increasingly stark and difficult-to-manage inequalities and fragmentation" (trend-based), "ecological transition and health promotion," "controlled technological development... to the extent possible," "globalized technological explosion," and "disasters and disorganization." Based on all the scenarios, key issues emerged: social and geographic health inequalities and vulnerability, accounting for the burden (economic and social weight) of diseases, understanding health in its two dimensions—individual and collective—the use of big data, the development of new technologies, the anticipation and detection of emerging issues (environmental, infectious, behavioral...), analysis of different geographic scales, and the integration of ethical considerations into the Institute’s work. For each of these challenges, needs were identified in terms of research, methodological development, partnerships, legal and ethical tools, training or recruitment, organizational development of the InVS, and foresight monitoring. Recommendations for continuing the forward-looking monitoring initiative were also proposed.