Targeted drug delivery with advanced precision therapeutics emerges at a fast rate through the integrating microbiota biomarkers and nanotechnology innovations. The research examines how combination diagnostics based on microbiome analysis work together with nanotechnology systems to develop powerful drugs which deliver more effective results while being safer. Drug metabolism significantly relies on the gut microbiota because it directly affects both pharmacological drug absorption patterns and therapeutic response. Touching microbiota-derived biomarkers helps researchers build individualized medical approaches which improves drug effectiveness and restricts adverse reactions. Scientists draw conclusions in this review about how microbiota-guided nanocarriers demonstrate effective results for treating oncology, infectious diseases, and metabolic disorders from studied case examples. Microbiota-guided nanoparticles deliver probiotics to treat diseases in the gastrointestinal tract and function as cancer therapy carriers and act as lipid-based systems that control immune system responses. The identified cases strongly demonstrate how a microbiome–nanotechnology combination can handle differences in therapeutic outcomes between patients. The adoption of microbiome–nanotechnology faces three main obstacles: regulatory barriers, complex formulation development, and the necessity of standardized microbiome analysis methods. Future research needs to optimize predictive models of microbiota and develop safe nanomaterials together with animal and human research translations to reach brand new levels of specificity that will establish next-generation personalized medicine.