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Abstract Transparent microelectrodes have recently emerged as a promising approach for crosstalk‐free multifunctional electrical and optical biointerfacing. High‐performance flexible platforms that allow seamless integration with soft tissue systems for such applications are urgently needed. Here, silver nanowires (Ag NWs)‐based transparent microelectrode arrays (MEAs) and interconnects are designed to meet this demand. The nanowire networks exhibit a high optical transparency >90.0% at 550 nm, and superior mechanical stability up to 100,000 bending cycles at 5 mm radius. The Ag NWs microelectrodes preserve low normalized electrochemical impedance of 3.4–15 Ω cm²at 1 kHz, and the interconnects demonstrate excellent sheet resistance (R_sh) of 4.1–25 Ω sq⁻¹. In vivo histological analysis reveals that the Ag NWs structures are biocompatible. Studies on Langendorff‐perfused mouse and rat hearts demonstrate that the Ag NWs MEAs enable high‐fidelity real‐time monitoring of heart rhythm during co‐localized optogenetic pacing and optical mapping. This proof‐of‐concept work illustrates that the solution‐processed, transparent, and flexible Ag NWs structures are a promising candidate for the next‐generation of large‐area multifunctional biointerfaces for interrogating complex biological systems in basic and translational research.