Wearable electrochemical biosensors for perspiration analysis offer a promising non-invasive biomarker monitoring method. Herein, a functionalized hybridized nanoporous carbon (H-NPC)-encapsulated flexible 3D porous graphene-based epidermal patch was firstly fabricated for monitoring sweat glucose, lactate, pH, and temperature using simple, cost-effective, laser-engraved, and spray-coating techniques. The fabricated H-NPC-modified electrode significantly increased electrochemical surface area and electrocatalytic activity. Within the physiological sweat range (0–1.5 mM), the second-generation glucose sensor exhibited an excellent sensitivity of 82.7 μAmM−1cm−2 with 0.025 μM LOD. Moreover, the lactate biosensor exhibited an extraordinary linear range (0–56 mM) response owing to the incorporation of an outer diffusion limiting layer (DLL) that controls the lactate flux reaching the enzyme with comparable sensitivity (204 nAmM−1cm−2) and LOD (4 μM). Finally, we employed an analytical correction approach incorporating pH and temperature adjustments during on-body tests. In addition to connecting various carbon-based materials to limitless metal-organic frameworks as a transduction material, our research also paves the way for enabling these sensors to operate on pH and T correction independently while delivering accurate results.