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Biomarker-based guided delivery of drugs is an emerging paradigm of precision medicine in which targeted therapeutic intervention is administered on the basis of certain biological markers in order to achieve maximal dosing, targeting, and time optimization. By utilizing quantifiable physiological or molecular signatures like the expression of transporters, enzymatic activities, metabolite levels, or disease-specific markers to tie in the correlation of drug disposition, these systems provide individualized intervention with optimized efficacy and safety. Oral administration of drugs is still the best route in patient compliance; however, several drugs are handicapped by suboptimal bioavailability secondary to poor solubility, limited permeability, efflux transporter participation, and enzymatic first-pass degradation. These result in variable therapeutic results in patient populations. Biomarker guidance in oral drug delivery provides a potent strategy for overcoming such challenges through site-specific release, real-time dose optimization, and adjustment of absorption pathways. Recent developments include pH-controlled formulations for gut-specific targeting, enzyme-activated nanocarriers, glucose-starved responsive devices for metabolic disease, and biomarker-driven transporters for permeability enhancement. Preclinical and early-phase clinical studies hold promising prospects for applications in oncology, infectious disease, inflammatory bowel disease, and metabolic disease. While promising momentum exists, transition to routine use in the clinic awaits rigorous biomarker validation, scalability in manufacture, and regulations harmonization. On the horizon, the integration of biomarker-guided oral drug delivery with nanotechnology, artificial intelligence, machine learning, and wearable biosensors holds promise for revolutionizing oral therapy into very personalized, responsive, and efficient treatment methods.