Thermal comfort is an important factor in designing energy-efficient indoor environments and enhancing occupant well-being. However, existing comfort models, such as PMV and 2-Node model, often neglect individual differences particularly gender-based variations in thermoregulation and localized thermal perception. This study investigates gender-specific differences in skin temperature and local thermal comfort under thermally neutral conditions. A controlled laboratory experiment was conducted involving 45 healthy participants (23 males and 22 females), aged 18–35, performing light office-like tasks in a climate-controlled chamber at an ambient temperature of 25.5 ℃. Skin temperature was continuously recorded at multiple body regions, and participants provided regular assessments of local thermal sensation and comfort. Statistical analyses revealed significant gender-based differences in local skin temperature, particularly in the extremities. Male participants exhibited higher temperatures in the hands, arms, legs, and feet, while female participants showed higher temperatures in the chest region. Large effect sizes were observed in the chest, lower leg, foot, and upper leg. Additionally, male participants reported a broader range of thermal comfort responses, whereas females reported consistently higher comfort levels. These differences were statistically significant across all analyzed body parts. The findings suggest that thermal comfort is not uniform and that gender-based physiological differences can lead to distinct thermal experiences. Incorporating such insights into thermal comfort modeling can improve prediction accuracy and promote more inclusive environmental control strategies. Personalized thermal management, especially through localized systems has the potential to enhance occupant satisfaction while maintaining energy-efficient indoor conditions.