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Tyre Pressure Monitoring System (TPMS) has been identified as one of the key emerging demands to be standardized in automotive industry, in which the microprocessor, radio frequency chip, pressure sensor, temperature sensor are the core components inside the wheel sensor module of the system. System-in-Package (SiP) technology is generally adopted to integrate the above mentioned chips in order to offer compact package size for wheel sensor miniaturization. Moreover, in view of the stringent reliability requirements and harsh working environment of the wheel sensor, leaded package format such as small-outlined package (SOP) is commonly employed to provide superior reliable performance. Nevertheless, unless System-on-Chip (SoC) is developed, multiple chip integration with increasing I/Os always imparts critical challenges to leaded packages due to the limitation of the routing flexibility of metal leadframe, not to mention a cavity is required for pressure sensor operation. Aiming to integrate the chips inside a leaded package without significantly increasing the size, a mixed organic substrate-metal leadframe approach was firstly implemented for TPMS-related applications. Instead of stacking up the chips which may increase the risk level of assembly, the chips were bonded on an organic substrate for signal redistribution. Numerical analysis has been performed to evaluate the stress level inside the package, and button shear test was performed to form the criteria in selecting the adhesives and mold compound for the SiP. Extensive reliability tests, including those application specific tests such as 30,000G constant acceleration test, 20-20KHz variable frequency vibration test, and 1,500G mechanical shock test, were performed to qualify the package. In addition, a low-cost pressure sensor calibration approach has also been introduced and the working principles and the performance will also be discussed in this paper.