The high prevalence of chronic diseases in urban slums poses increasing challenges to future social and economic development for these disadvantaged areas. Assessing the health status of slum residents offers guidance for formulating appropriate policies and interventions to improve slum residents’ health outcomes. This research aimed to identify the social determinants of chronic diseases reporting among slum dwellers in Egypt. A cross-sectional survey was conducted from March to December 2021 in three slum areas in Giza governorate, Egypt, including 3,500 individuals. We constructed an asset index and a welfare index to measure the economic status and living conditions of slum residents, respectively. We used these indices, along with demographic and socio-economic factors, as independent variables in the analysis. We modeled factors associated with health status using a two-level mixed logistic model to control the effects of slum areas and the potential correlation between household members. The study contributed significantly to a better understanding of the context in which slum dwellers live and the interlinkages among poor living conditions, low economic status, and health outcomes. The results showed a high rate of self-reported chronic diseases among adults aged 18 and older, reaching more than 22%, while it did not exceed 2.0% among children in the slum areas. Therefore, measuring the determinants of chronic diseases was limited to adults. The sample size was 2530 adults after excluding 970 children. The prevalence of chronic diseases among adults ranged between 16.3% in Zenin and 22.6% in Bein El Sarayat. Our findings indicated that low socio-economic status was significantly associated with reporting chronic diseases. Future policies should be dedicated to improving living conditions and providing necessary healthcare services for these vulnerable areas.