A Raman-based resection system and methods of operation thereof are disclosed. The method includes producing, via an ablation laser, an interrogation electromagnetic radiation over a scanning point of a sample having been treated with a Raman reporter, the ablation laser illuminating the scanning point at an interrogation power level acquiring, via a detector, a signal indicative of scattered photons emanating from the scanning point following the illumination determining, via a processor, whether the acquired signal is indicative of the presence of the Raman reporter in and/or upon the scanning point and, responsive to a determination of the presence of the Raman reporter in and/or upon the scanning point, producing, via the ablation laser, an ablation electromagnetic radiation over the scanning point to ablate tissue at the scanning point, wherein the ablation electromagnetic radiation is at a power level sufficient to ablate tissue.