Independent of total body fat mass, predominant upper body fat mass distribution is strongly associated with cardio-metabolic comorbidities. However, the mechanisms underlying fat mass localization are not fully understood. Although a large body of evidence indicates sex-specific fat mass distribution, women are still excluded from many physiological studies and their specific features have been investigated only in few studies. Moreover, endurance exercise is an effective strategy for improving fat oxidation, suggesting that regular endurance exercise could contribute to the management of body composition and metabolic health. However, no firm conclusion has been reached on the effect of fat mass localization on fat oxidation during endurance exercise. By analyzing the available literature, this review wants to determine the effect of fat mass localization on fat oxidation rate during endurance exercise in women, and to identify future research directions to advance our knowledge on this topic. Despite a relatively limited level of evidence, the analyzed studies indicate that fat oxidation during endurance exercise is higher in women with lower upper-to-lower-body fat mass ratio than in women with higher upper-to-lower-body fat mass ratio. Interestingly, obesity may blunt the specific effect of upper and lower body fat mass distribution on fat oxidation observed in women with normal weight during endurance exercise. Studying and understanding the physiological responses of women to exercise are essential to develop appropriate physical activity strategies and ultimately to improve the prevention and treatment of cardio-metabolic diseases.