Molecular endoscopy represents a transformative advance in the detection, diagnosis, and management of gastrointestinal diseases, addressing the critical limitations of conventional techniques. Current diagnostic standards, such as white light endoscopy (WLE), often fail to detect early-stage lesions, particularly in high-risk populations like Barrett's esophagus or inflammatory bowel disease patients. To overcome these challenges, molecular endoscopy, using fluorescent molecular probes, may offer ultimate precision by targeting disease-specific biomarkers. Technologies like Confocal Laser Endomicroscopy (CLE) and Immunoendoscopy are revolutionizing in vivo diagnostics, enabling the real-time visualization of tissue microarchitecture and physiological mechanisms. Fluorescence molecular endoscopy (FME) enhances the detection of precancerous and cancerous lesions, even those undetectable by conventional methods, by highlighting subtle molecular changes. Clinical applications include early tumor detection, therapy response monitoring, and improved lesion characterization. Despite these advancements, challenges persist, including high costs, a lack of standardization, and the need for specialized training. Recent innovations, such as a multi-parametric rigid standard, aim to ensure the reliable performance assessment and quality control of FME systems, addressing subjective variability and improving reproducibility. In addition, the integration of artificial intelligence (AI) with molecular endoscopy offers the potential to further reduce detection errors and significantly enhance diagnostic accuracy. This advancement underscores the potential of molecular endoscopy for personalized GI disease management, while highlighting the need for ongoing research to refine the technology, validate its clinical utility, and overcome the barriers to routine clinical application.