Abstract Real‐time tracking of protein biomarkers in dermal interstitial fluid (ISF) remains a significant challenge due to the limitations in robust analyte sensing, efficient ISF extraction, and seamless system integration. Herein, a wearable microneedle patch (w‐MN patch) integrated with a metal hydrogel‐based electrochemical probe is demonstrated for simultaneous sampling and monitoring of immunoglobulin G (IgG), a key protein biomarker, in ISF. The sensing probe, featuring ferrocene anchored on polydopamine functionalized‐Au gel, enables highly stable and sensitive detection with an ultralow detection limit of 0.05 ng mL ‒1 in both in vitro and ex vivo models. A hollow MN (HMN) array design facilitates rapid ISF collection, yielding 5.6 µL within 5 min in a live rat model, as validated by simulations and experimental data. By integrating the HMN array via a sensing chip using a home‐made packaging chamber, the w‐MN patch realizes real‐time, wireless IgG monitoring in vivo. This work presents a fully integrated platform that unites sensitive protein biomarker detection, efficient ISF extraction, and wearable device engineering, offering significant potential for precision diagnostics and next‐generation wearable healthcare technologies.