In this study, we disentangle the complex relationship between structural and intermediary social determinants of health in Andalusia (Spain) after the period of economic downturn, with the aim to understand the factors that might be addressed to reduce future health inequalities in socioeconomically vulnerable regions. Data from the IMPACT-A project were used. Our sample included 1200 individuals randomly selected using a stratified sampling process according to gender, age group and eight provinces in Andalusia (Spain). Structural equation modeling was conducted to test the goodness of fit of our data with the previous theoretical background. Our results indicated that socioeconomic factors and demographics are associated to health by influencing lifestyles, socioeconomic experiences during the crisis, and personal wellbeing. Additionally, several remarkable contributions from the results can be highlighted: (a) important differences in health outcomes were found in Andalusian females, (b) there was no relationship between income and lifestyles, © people with unmet medical needs demonstrated a higher perception of social discrimination, and (d) discrimination and happiness had a mediating effect on health. The final model accounts for more than one-third of the variance in health and describes the complex association of social determinants that might be addressed to reduce inequities in health in this region.