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Abstract Tissue interfaced electronics have become promising candidates for transcending beyond conventional diagnostic technology, enabling chronic, quantitative health monitoring possibilities; however, these systems have primarily relied on impenetrable materials that contribute to the mechanical and physical mismatch of bioelectronic interfaces. Inspired by the soft mechanics and physical architecture of the epidermal extracellular matrix, this study presents a 3D microporous, fibrous mesh of polydimethylsiloxane for epidermal electronics. The resulting elastic microfiber mat, exhibits a minimal mechanical footprint with analogous viscoelastic behavior, cytocompatibility, and biofluid‐permeable interface capable of small molecule, gas, and transdermal water diffusion. Electrocardiography electrodes heterogeneously integrate within the synthetic electronic‐extracellular matrix (e‐ECM) membrane and achieve chronic high resolution biopotential monitoring during typically debilitating environments (e.g., vigorous sweating) for conventional bioelectronics. The e‐ECM platform provides a substrate template for open‐mesh electronics, enabling advanced implementations in long‐term quantitative analysis monitoring for wearable and implantable devices.