A new multi-physics finite element model (FEM) on the vibration of the radial artery on the wrist is built by this study to predict vibration of wrist artery vessel vibration and then diastolic and systolic blood pressures. The FEM includes the sensor of gel capsule and strain-sensing electrodes, skin, bones and muscles. The vibrations of skin surface and the sensor module are successfully simulated by the established FEM. The resulted vibratory deformation of the sensor electrodes are further transformed to resistance variations to mimic realistic electronics of the front-end readout circuit via establishing a cross-discipline sub-FEM model. The established FEM can is particularly customized to varied ages, weights, heights, genders, and special cardiovascular diseases of users. The customization can be performed in a fashion of one-time calibration by medical staff and/or medical staff. With the customized FEM in high accuracy level, the diastolic and systolic pressures can be accurately predicted by the simulated output resistance variation. Based on simulation FEMs, the design of the pulse sensor is successfully optimized via the processes of Taguchi and numerical methods. The measurements are also conducted to a dozen of subjects. It shows that the designed novel blood pressure sensor is capable of sensing the blood pressure to require accuracy level of the error less than 10% as compared to commercial counterparts with a cumbersome cuff.