This review explores sex- and gender-related differences in obesity, focusing on biological, behavioral, and sociocultural factors influencing obesity development and its clinical implications. Obesity is a multifactorial disease with increasing global prevalence, and while women are more likely to become obese than men, they often face greater psychological risks and less effective weight loss interventions. The review highlights differences in body composition, fat distribution, energy expenditure, and the role of sex steroid hormones, gut microbiota, and genetic factors in obesity. Women tend to store fat in gluteofemoral depots, while men store more visceral fat, which is linked to higher metabolic risks. Sex hormones, such as estrogen and testosterone, influence fat distribution, energy metabolism, and appetite. Women generally have higher brown adipose tissue activity and greater thermogenic capacity, which may protect against obesity. However, the consequences of these differences on metabolic disease progression remain unclear. Genetic factors also contribute to sex-specific obesity susceptibility, with some loci showing stronger effects in females. Gut microbiota composition varies by sex, with females having higher Bacteroidetes and males higher Firmicutes, which may influence metabolic health. Behavioral and sociocultural factors, including food preferences, eating habits, and societal pressure, also contribute to sex differences in obesity. Women are more susceptible to body dissatisfaction and eating disorders, while men are less likely to seek weight loss interventions. Clinical implications include sex-specific risks for comorbidities such as diabetes, hypertension, and cancer, with females facing greater psychological and metabolic risks. Weight loss interventions show gender differences in effectiveness, with women often responding less well to certain treatments. The review emphasizes the need for sex- and gender-specific approaches in obesity research and treatment.This review explores sex- and gender-related differences in obesity, focusing on biological, behavioral, and sociocultural factors influencing obesity development and its clinical implications. Obesity is a multifactorial disease with increasing global prevalence, and while women are more likely to become obese than men, they often face greater psychological risks and less effective weight loss interventions. The review highlights differences in body composition, fat distribution, energy expenditure, and the role of sex steroid hormones, gut microbiota, and genetic factors in obesity. Women tend to store fat in gluteofemoral depots, while men store more visceral fat, which is linked to higher metabolic risks. Sex hormones, such as estrogen and testosterone, influence fat distribution, energy metabolism, and appetite. Women generally have higher brown adipose tissue activity and greater thermogenic capacity, which may protect against obesity. However, the consequences of these differences on metabolic disease progression remain unclear. Genetic factors also contribute to sex-specific obesity susceptibility, with some loci showing stronger effects in females. Gut microbiota composition varies by sex, with females having higher Bacteroidetes and males higher Firmicutes, which may influence metabolic health. Behavioral and sociocultural factors, including food preferences, eating habits, and societal pressure, also contribute to sex differences in obesity. Women are more susceptible to body dissatisfaction and eating disorders, while men are less likely to seek weight loss interventions. Clinical implications include sex-specific risks for comorbidities such as diabetes, hypertension, and cancer, with females facing greater psychological and metabolic risks. Weight loss interventions show gender differences in effectiveness, with women often responding less well to certain treatments. The review emphasizes the need for sex- and gender-specific approaches in obesity research and treatment.