A wearable electrochemical biosensor for real-time monitoring of neurotransmitters in sweat during physical exercise is presented. The biosensor utilizes a CuMOF@InMOF architecture, enhanced with gold nanoparticles (AuNPs), to improve electron transfer, surface area, and overall stability. Thiolate nucleic acid aptamers, highly specific to dopamine, serotonin, and epinephrine, are immobilized on the biosensor surface, enabling precise and simultaneous detection of these key neurotransmitters. The flexible, multi-electrode platform is integrated into a microfluidic patch that adheres to the skin, facilitating seamless sweat collection and continuous neurochemical analysis. Structural validation confirmed the successful synthesis of the CuMOF@InMOF architecture with enhanced surface area, stability, and electron transfer properties, contributing to the biosensor's high sensitivity and selectivity. Impressively, the biosensor achieved detection limits of 0.18 nM for dopamine, 0.33 nM for serotonin, and 0.27 nM for epinephrine, with a broad dynamic range from 1 nM to 10 µM. Performance was validated through square wave voltammetry and amperometry, demonstrating exceptional sensitivity, selectivity, and stability. This innovative biosensor offers a powerful tool for non-invasive, real-time neurochemical monitoring, with significant potential in personalized healthcare.