Wearable electrochemical biosensors have catalyzed a shift toward personalized medicine and are gaining commercial traction, largely because they can deliver high specificity and sensitivity using operationally simple, rapid, portable, low-cost, and compact formats that support continuous, real-time analysis with user-friendly workflows. Concurrent advances in multitechnology biosensing architectures and scalable manufacturing have accelerated the development of lab-on-a-chip systems and wearable devices capable of interrogating health-relevant chemical signals at the molecular level. Nevertheless, the functional ceiling of many wearable platforms remains constrained by insufficiently selective recognition of target biomolecules, a deficiency that can propagate cross-reactivity, compromise analytical fidelity in complex biofluids, and ultimately limit clinical interpretability and adoption. Addressing this limitation requires more rigorous integration of molecular recognition strategies with electrode design, including interface engineering that preserves bioreceptor activity while suppressing nonspecific interactions under dynamic on-body conditions. In this context, progress in nanomaterials has enabled the coupling of nanomaterial-enabled electrochemical transduction with wearable electrodes to improve signal generation and interfacial control. This review introduces key electrochemical biointerfaces and core electroanalytical modalities (voltage, amperometry, and impedance techniques), emphasizing their translation to wearable formats for biofluid analysis. It further provides a critical analysis of integrated multitechnology wearable biosensor platforms, highlighting design considerations and performance trade-offs that inform next-generation systems for biomolecular detection.