Gender inequalities in health-related quality of life (QoL) are generally few and small, even in large surveys. Many generic measures limit assessment to QoL overall and its physical and psychological dimensions, while overlooking internationally important environmental, social, and spiritual QoL domains. Unique cross-cultural legacy data was collected using four WHOQOL-100 surveys of adults living in 43 cultures world-wide (17,608 adults; ages 15-101). It was first used to examined gender profiles of its five QoL international domains, and their component facets. Few significant gender differences (p < .001) were found. Women reported higher spiritual QoL than men on faith, and spiritual connection facets specifically. Men reported higher physical and psychological QoL domains than women. We aimed to identify those QoL dimensions that contribute to women's overall QoL in health, as this information could inform gender inequalities interventions in health. Environmental QoL explained a substantial 46% of women's overall QoL and health (n = 5,017; 17 cultures) (stepwise multiple regression adjusted for age, education, and marital status covariates). Five environmental QoL facets contributed significantly to this result; home environment offered most explanation. Age band analysis was conducted to understand when interventions might be best timed in the lifespan to improve women's QoL. Younger women (< 45 years) reported the poorest QoL across the lifetime, and on every domain. After 45, all domains except physical QoL increased to very good at about 60, and high levels were sustained beyond 75, especially environmental QoL. Global findings show that assessing environmental, social, and spiritual QoL domains are key to fully understanding women's QoL and health. These assessments should be prioritized in surveys that aim to improve international conservation, and public health policies.