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Midsoles are important components in footwear as they provide shock absorption and stability, thereby improving comfort and effectively preventing certain foot injuries. A strategically engineered midsole designed to mitigate plantar pressure can enhance athletic performance and comfort levels. Despite the importance of midsole design, the potential of using in-plane density gradation (deliberate variation of material density across the horizontal plane) in midsoles has been rarely explored. The present work investigated the effectiveness of in-plane density gradation in shoe midsoles using novel polyurea foams as the material candidate. Different polyurea foam densities, ranging from 95 to 350 kg/m²were examined and tested to construct density-dependent correlative mathematical relations required for optimizing the midsole design for enhanced cushioning and reduced weight. This study combined mechanical testing and plantar pressure measurements to validate the efficacy of density-graded midsoles. The methodology introduced here is relevant to realistic walking conditions, ensured by biomechanical tests supplemented by digital image correlation analyses. An optimization framework was then created to allocate foam densities at certain plantar zones based on the required cushioning performance constrained by the local pressure. The optimization algorithm was specifically tailored to accommodate varying local pressures experienced by different areas of the foot. The optimization strategy in this study aimed at reducing the overall weight of the midsole while ensuring there were no compromises in cushioning efficacy or distribution of plantar pressure. The approach presented herein has the potential to be applied to a wide range of gait speeds and user-specific plantar pressure patterns.