Aim: This study aims to evaluate the impact and potential of advanced metabonomic technologies in enhancing surgical decision-making and patient outcomes, focusing on oncological and critical care settings. Methods: A comprehensive review of literature was conducted to gather and analyze data on the application of MAS-NMR spectroscopy, mass spectrometry imaging (MSI), and rapid evaporative ionization mass spectrometry (REIMS) in surgical contexts. Studies encompassing tumor margin assessment, intraoperative tissue characterization, and metabolic profiling in critical illness were reviewed to synthesize current findings and technological advancements. Results: MAS-NMR spectroscopy demonstrated high sensitivity in distinguishing between benign and malignant tissues, offering rapid and accurate intraoperative guidance. MSI provided histologically specific molecular profiles, enhancing surgical precision in tumor resections. REIMS enabled real-time tissue analysis during surgery, facilitating immediate decision-making based on molecular composition. These technologies showed promise in predicting patient outcomes, optimizing therapeutic strategies, and minimizing surgical complications. Conclusion: Advanced metabonomic technologies represent a paradigm shift in surgical practice, offering precise, real-time molecular insights that improve diagnostic accuracy and therapeutic efficacy. Integration of MAS-NMR spectroscopy, MSI, and REIMS enhances surgical decision-making in oncology and critical care, paving the way for personalized treatment approaches and improved patient outcomes.