Reducing under-five mortality is a crucial indicator of overall development in a country. However, in Angola, understanding the factors contributing to hospital deaths in this vulnerable demographic remains incomplete despite improvements in healthcare infrastructure and public health policies. With one of the highest under-five mortality rates in sub-Saharan Africa, Angola faces significant challenges such as malaria, malnutrition, pneumonia, neonatal conditions, and intestinal infectious diseases, which are the leading causes of death among children. This study aimed to identify factors associated with hospital deaths among children aged 28 days to five years admitted to DBPH in Luanda between May 2022 and June 2023. Using a hospital-based case-control design, the study included 1020 children, among whom 340 experienced hospital deaths. Distal and intermediate determinants emerged as primary predictors of hospital mortality, showing significant associations with: mother without schooling (OR [95%CI] 4.3 [1.2-15.7], p < 0.027); frequent alcohol consumption during pregnancy (OR [95%CI] 3.8 [2.5-5.9], p < 0.001); hospital stay ≤24 h (OR [95%CI] 13.8 [6.2-30.8], p < 0.001); poor nutritional status (OR [95%CI] 2.1 [1.4-3.2], p < 0.001); short interbirth interval (OR [95%CI] 1.7 [1.1-2.5], p < 0.014); maternal age ≤19 years (OR [95%CI] 5.6 [3.0-10.8], p < 0.001); and maternal age ≥35 years (OR [95%CI] 2.1 [1.2-3.7], p < 0.006). These findings highlight the preventable nature of most under-five hospital deaths and underscore the urgent need to address social inequities and improve the quality of primary healthcare services to effectively reduce child mortality in Angola.