Background: Research addressing the impact of a large number of factors on unemployment is scarce. We aimed to comprehensively identify factors related to unemployment in a sample of persons aged 18â64 from Finland, Poland and Spain. Methods: In this cross-sectional study, factors from different areas were considered: socio-demographic indicators, health habits, chronic conditions, health state markers, vision and hearing indicators, and social networks and built environment scores. Results: Complete data were available for 5003 participants, mean age 48.1 (SD 11.5), 45.4% males. The most important factors connected to unemployment were health status indicators such as physical disability (OR = 2.944), self-rated health (OR = 2.629), inpatient care (OR = 1.980), and difficulties with getting to the toilet (OR = 2.040), while the most relevant factor related to employment were moderate alcohol consumption (OR = 0.732 for non-heavy drinkers; OR = 0.573 for infrequent heavy drinkers), and being married (OR = 0.734), or having been married (OR = 0.584). Other factors that played a significant role included presence of depression (OR = 1.384) and difficulties with near vision (OR = 1.584) and conversation hearing (OR = 1.597). Conclusions: Our results highlight the importance of selected factors related to unemployment, and suggest public health indications that could support concrete actions on modifiable factors, such as those aimed to promote physical activity and healthy behaviors, tackling depression or promoting education, in particular for the younger.