An observational cross-sectional study was conducted in a group (n = 371) of fertile age women with endometriosis, by administering a structured questionnaire, in order to evaluate the incidence of gynecological and systemic comorbidities and the impact on quality of life (QoL) in two different groups of Italian and Chinese patients affected by endometriosis. Chinese (n = 175) and Italian (n = 196) women were compared regarding systemic (inflammatory, autoimmune, and mental) and gynecological comorbidities, pain symptoms, and QoL, by using the Short Form 12 (SF-12). Italian patients resulted younger at the diagnosis and suffered more frequently from severe pain than Chinese ones. Deep infiltrating endometriosis (DIE) and mixed phenotypes were more frequent in Italian patients, whereas ovarian (OMA) and superficial endometriosis (SUP) were more common in the Chinese. The Italian group showed more systemic comorbidities, and those disorder were already present before the diagnosis of endometriosis. Furthermore, the Italian group showed lower SF-12 physical and mental scores, suggesting a worse health-related QoL in Italian endometriotic patients. A number of differences has been observed between Italian and Chinese women with endometriosis in terms of comorbidities and QoL, which may be related to the ethnicity, the different health system organization and the social and cultural background.