Background The unplanned urbanization in Jordan has over time created many informal settlements “slums” around big cities as Amman, Zerka and Aqaba. The purpose of this study was to highlight the most common challenges related to social determinants of health in two selected slum areas in Amman and Aqaba and suggest policy directions and interventions to meet these challenges. Methods In addition to a prestructured interview with all household heads living in the two slum sites, focus group meetings with a purposefully selected sample of 12 slum dwellers in each site were used to assess the structural and intermediary determinants of health as perceived by slum residents in the two study locations. Results The study found that slum residents in the two locations suffer from many challenges as severe poverty; unemployment; illiteracy and low education attainments; gender discrimination; insufficient and poor diet; social and official exclusion; unhealthy environment; lack of water supply, electricity and basic sanitation facilities; high prevalence of diseases; and insufficient and inappropriate health services. Specific policy directions to meet these challenges were recommended and grouped into three main clusters: social protection, social inclusion and empowerment. Conclusion New plans and tools should be developed by local authorities in Jordan to understand, protect, include and empower those vulnerable people who are forced to live in these unhealthy and inhuman environments. Copyright © 2014 John Wiley & Sons, Ltd.