The aim of this study was to determine the separate and joint contribution of individual, family, occupational, and social factors in explaining the life satisfaction of working mothers of children with developmental disabilities. Working mothers of children with disabilities participated in this study (N = 508). They completed an online questionnaire to measure factors from personal (optimism and personal strength), family (satisfaction with family finances, parental stress, number of children, and support from family members related to work), work (job demands, control, and support) and society domain (satisfaction with the healthcare, educational and welfare system). All of them were employed (at least part-time) but also, they all had at least one child with disabilities under 19 years of age whose degree of disability was officially determined. Regression analysis indicated that factors from personal, family (satisfaction with family finances, parental stress, and support from family members related to work), and societal domain (satisfaction with the healthcare system) predicted mothers’ life satisfaction. Work-related variables did not. A comprehensive approach is very useful in studying the well-being of parents of children with disabilities. Future studies should also include fathers, as it is reasonable to assume that mothers and fathers differ in the influence of certain factors on their well-being. Considering the sample size and bias, these results have significant limitations in terms of generalizability.