Human hands are among the most vulnerable body parts when it comes to cold injury. They play a crucial role in motor performance and work efficiency. However, the current understanding of the hand’s heat transfer and thermoregulation is rather limited, making it difficult to accurately assess hand thermal responses. Without this knowledge, the promise to improve health, comfort, and work efficiency through science-based improvements in product design and engineering of personal protective equipment (PPE) will likely remain unfulfilled. Numerical models of hand thermoregulation provide an efficient, cost-effective, and safe way to investigate mechanisms of hand thermal responses under different environmental conditions while testing different physiological parameters.Three-dimensional (3D) computational models are valuable tools to study the temporal and spatial dynamics of heat transfer, airflow, and hand skin temperature evolution under different environmental scenarios. The overall purpose of this study is to develop a 3D multi-segment hand-specific thermal model with realistic hand geometry, anatomy, and thermo-physical and physiological properties to predict the heat transfer and thermal response of the hand under different environmental conditions. The model consists of 1) a computational fluid dynamics (CFD) model with realistic hand geometry to investigate the heat transfer and airflow around the hand when exposed to different wind scenarios, 2) regression models to link the convective heat transfer coefficient (h_c) with ambient wind speed and direction for both the whole hand and individual hand segments, and 3) a mechanistic 3D multi-segment hand-specific thermoregulation model to systematically evaluate the physiological and thermal responses of the hand during cold exposure. The CFD model begins with a 3D surface scan of a thermal hand manikin. The obtained virtual hand model is then divided into 17 segments: the forearm, palm, dorsal, and five fingers, with each finger further divided into fingertip, middle segment, and finger root, except for the thumb which only consists of a tip and root. The heat transfer and airflow between the hand skin and environment are calculated based on the finite volume method using the ANSYS FLUENT fluid simulation software (Ansys Inc., USA). A wind tunnel is developed for the thermal hand manikin to measure the hand skin's heat flux under various wind scenarios. The simulated heat flux is compared with the measured data and shows good conformity. The model results show that the h_c varies significantly depending on the specific location and as a function of the local geometry of the hand. The h_c of fingers are larger than those of the forearm, palm, and dorsal. Fingertips, and especially the tip of the little finger, are the segments that are most vulnerable to heat loss. While the effect of wind direction on the h_c of the hand as a whole appears negligible, it plays a significant role with regard to individual hand segments. The h_c of both the whole hand and individual hand segments increase exponentially with wind speeds. Finally, regression models of the h_c on wind speed for both the whole hand and each hand segment under different wind directions are derived based on the numerical results. The virtual hand model developed in the CFD model is adopted in the 3D multi-segment hand-specific thermoregulation model. Besides, a virtual hand skeleton geometry, obtained through a 3D surface scan of a physical hand skeleton model, is incorporated into the virtual hand model. The virtual hand-skeleton model is also divided into 17 segments. Each segment has a bone core and an outer soft tissue layer composed of muscle, fat, and skin. The thermo-physical and physiological properties of each segment and layer are obtained from a photogrammetric analysis of anatomic atlases extracting the known properties of bone, muscle, fat, and skin. Cold-induced vasodilation (CIVD) at the fingertip is simulated by superimposing symmetrical triangular waveforms to the basal blood flow rate. Heat transfer throughout the hand by metabolism, blood perfusion, and conduction between each segment and layer is also incorporated as are heat losses from the hand’s skin by convection and radiation as well as protective effects of gloves. The model predicts the thermal response for both the whole hand and various hand locations based on environmental conditions, glove material properties, design features, as well as the anthropometric, anatomical, physiological, and thermo-physical parameters used. This study is highly interdisciplinary and draws on a range of scientific fields that include human and environmental science, computing technology, numerical methods, fluid dynamics, image processing, and statistics. The outcomes of this dissertation are therefore expected to have a broad impact in a range of areas including PPE where it will contribute to enhancing the wearers’ working efficiency, safety, and health.