In recent years, flexible and sensitive pressure sensors are of extensive interest in healthcare monitoring, artificial intelligence, and national security. In this context, we report the synthetic procedure of a three-dimensional (3D) metal-organic framework (MOF) comprising cadmium (Cd) metals as nodes and isoniazid (INH) moieties as organic linkers (CdI2-INH=CMe2) for designing self-polarized ferroelectret-based highly mechano-sensitive skin sensors. The as-synthesized MOF preferentially nucleates the stable piezoelectric beta-phase in poly(vinylidene fluoride) (PVDF) and also gives rise to a porous ferroelectret composite film. Benefiting from the porous structure of 3D MOFs, composite ferroelectret film-based ultrasensitive pressure sensor (mechano-sensitivity of 8.52 V/kPa within 1 kPa pressure range) as well as high-throughput ( power density of 32 mu W/cm(2)) mechanical energy harvester (MEH) has been designed. Simulation-based finite element method (FEM) analysis indicates that the geometrical stress confinement effect within the interpore region of the ferroelectret structure synergistically influences the mechano-electrical property of the MEH. In addition, 143 pC/N (similar to 4.5 times higher than commercial piezoelectric PVDF films) piezoelectric charge coefficient (d(33)) magnitude and superior response time (t(r) similar to 8 ms) of this composite ferroelectret film enable the detection of different physiological signals such as coughing, pronunciation, and gulping behavior, making it a promising candidate for early intervention of healthcare, which may play a significant role in accurate alert of influenza and chronic obstructive pulmonary disease (COPD)-related symptoms. In addition, MEH enables the tracking of the subtle pressure change in the wrist pulse, indicating its usefulness in effective mechanosensitivity. Since the cardiovascular signal is one of the vital parameters that can determine the on-going physiological conditions, the wireless transmission of the detected wrist pulse signal has been demonstrated. All of these features coupled with wireless data transmission indicate the promising application of MOF-assisted composite ferroelectret films in noninvasive real-time remote healthcare monitoring.