Background: Endometriosis is a chronic condition affecting physical health, emotional well-being, and socioeconomic stability. While pain is a well-recognized determinant of health-related quality of life (HR-QoL), the role of pain experience over employment status remains underexplored. Objective: To determine among women with endometriosis whether employment status independently contributes to HR-QoL, beyond clinical symptoms. Methods: This cross-sectional study was conducted at the University Hospital of Geneva. Women with a confirmed diagnosis of endometriosis were included. Employment status was categorized as full-time employment (>80%), part-time employment (≤80%), voluntary unemployment, and involuntary unemployment. HR-QoL was measured using the Endometriosis Health Profile-30 (EHP-30). Results: A total of 324 patients were included (mean age 32 ± 7.2 years); 78.2% had deep infiltrating endometriosis, and 34.5% reported prior surgery. Regarding employment, 63.2% were employed (51.5% full-time, 11.7% part-time), while 36.7% were unemployed, including 26.2% by choice. Full-time and part-time employment were linked to lower EHP-30 pain scores, with part-time employment showing a stronger association (β = -34.48, 95% CI: -58.00 to -10.88, p = 0.006) than full-time employment (β = -20.57, 95% CI: -40.70 to -0.43, p = 0.046). Unemployed women actively seeking work exhibited worse HR-QoL, particularly in social support (β = 34.95, 95% CI: 1.89 to 70.80, p = 0.048) and overall HR-QoL burden (β = 168.27, 95% CI: 30.60 to 205.91, p = 0.019). Conclusion: Employment status is an independent predictor of HR-QoL in women with endometriosis. Beyond pain, professional identity and social integration play key roles in endometriosis burden.