This review explores sex- and gender-related differences in obesity, focusing on biological, genetic, and sociocultural factors. It highlights that while women have a higher prevalence of obesity, they are more vulnerable to psychopathology, whereas men are less likely to pursue weight loss interventions and are more susceptible to metabolic complications. The review discusses the differential body composition and fat distribution between men and women, with females having higher total body fat but lower visceral adipose tissue (VAT) compared to males. It also examines the role of sex steroid hormones, such as estrogen and testosterone, in regulating energy expenditure, fat distribution, and metabolic health. Additionally, the review covers the impact of gut microbiota diversity on obesity, the neuroadaptive changes in food intake preferences, and the sociocultural factors influencing obesity development. Finally, it discusses the clinical implications of these sex- and gender-related differences, including the varying risks of obesity-related comorbidities and the effectiveness of weight loss interventions.This review explores sex- and gender-related differences in obesity, focusing on biological, genetic, and sociocultural factors. It highlights that while women have a higher prevalence of obesity, they are more vulnerable to psychopathology, whereas men are less likely to pursue weight loss interventions and are more susceptible to metabolic complications. The review discusses the differential body composition and fat distribution between men and women, with females having higher total body fat but lower visceral adipose tissue (VAT) compared to males. It also examines the role of sex steroid hormones, such as estrogen and testosterone, in regulating energy expenditure, fat distribution, and metabolic health. Additionally, the review covers the impact of gut microbiota diversity on obesity, the neuroadaptive changes in food intake preferences, and the sociocultural factors influencing obesity development. Finally, it discusses the clinical implications of these sex- and gender-related differences, including the varying risks of obesity-related comorbidities and the effectiveness of weight loss interventions.