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Conventional clinical monitoring of anesthetic agents predominantly relies on indirect physiological indicators, which fail to accurately quantify the actual anesthetic concentrations in circulating blood. We report a surface-enhanced Raman spectroscopy (SERS) sensing platform based on TiO₂@Ag nanocomposites, coupled with optimized solid-phase extraction pretreatment, for the semi-quantitative trend monitoring of anesthetic drugs in complex blood matrices. This platform achieves reliable detection across the clinically relevant concentration range (nanomolar to micromolar levels), enabling concentration-dependent detection of four widely used clinical anesthetic agents with excellent reproducibility. Validation with authentic clinical blood samples further confirms a significant correlation between recorded SERS signals and LC-MS/MS-determined laudanosine concentrations, together with physiologically consistent trends in pharmacodynamic responses. Collectively, these proof-of-concept findings support the preliminary feasibility of SERS-based intraoperative anesthetic monitoring, warranting further validation toward future perioperative drug monitoring applications.