Abstract: Recent awareness of the wide variability in medical practitioner performance drives a pressing need for improving medical technologies to ensure accurate diagnoses and expansion of the number of effective treatment options for patients. Additionally, current medical practices often focus on localized symptoms rather than systemic observations, and snapshots in time rather than continuous monitoring. Our goal was to develop a minimally invasive, implantable, pressure sensing system that continuously monitored physiological changes in real time. Specifically, we aimed to develop a system to monitor pressure changes in the upper urinary tract per degree of obstruction in the ureters. This study was conducted by integrating a MEMS pressure sensor and wireless sensor network into minimally invasive biocompatible packaging. A MEMS pressure sensor served to measure the accurate renal pelvic and bladder pressures while keeping the profile minimally invasive. Mica2Dot, the sensor network platform, was used to control the signal conditioning, current consumption, and wireless signal transmission. MEMS passivation and catheter packaging techniques were adapted to improve biocompatibility and surgical adaptability. System components were rigorously tested and verified for their electrical and system performance in simulated environments. During this iterative process, key findings from this study included the direct correlation of DC drift and excitation duty cycle. Lower duty cycle pulsatile excitation scheme was demonstrated to reduce drift. The parylene/silicone dual layer passivation was demonstrated to accentuate the system mechanical properties, biocompatibility, and surface property malleability. Furthermore, parylene as the passivation material for the transmitting circuit reduced the antenna dimension and improved transmitting performance through physiological tissues. After system integration, we tested our prototype in a porcine model. The system gateway received internal information while the system was fully implanted and when the subject was fully awake and active. These key findings demonstrated the possibility of utilizing this implantable sensor network as the platform technology to improve the understanding of human physiology, including intracranial, cardiac, and ophthalmological pressures on a long-term basis.