Multimodal SERS Biosensing Platforms: Emerging Opportunities for Ultrasensitive Biomarker Detection and Intelligent Diagnostics

Surface-enhanced Raman scattering (SERS) has emerged as a powerful analytical technique for biosensing owing to its ultrahigh sensitivity and molecular fingerprinting capability. However, the practical deployment of single-modality SERS is often hindered by signal fluctuations, matrix interference, and limited quantitative robustness in complex biological environments. To address these intrinsic limitations, multimodal SERS strategies have gained increasing attention by integrating SERS with complementary transduction modalities, enabling enhanced analytical reliability, internal cross-validation, and multidimensional biochemical profiling. In this review, we present a framework-driven and application-oriented overview of multimodal SERS biosensing, systematically covering fundamental design principles, nanomaterial engineering, and representative multimodal coupling strategies, including combinations with colorimetric (CM), fluorescence (FL), electrochemical (EC), and so forth. Rather than treating multimodality as a simple signal addition, we critically analyze how distinct modalities contribute complementary or synergistic information across different sensing scenarios. Furthermore, recent advances in integrated devices, microfluidic platforms, and data-driven analysis are discussed as key enablers for translating complex multimodal outputs into actionable diagnostic information. Importantly, we reorganize reported multimodal SERS systems according to major classes of disease-related biomarkers, highlighting how the choice of modality combinations should be guided by biomarker properties and clinical task requirements rather than by technological complexity alone. Finally, current challenges and future perspectives are outlined from the viewpoints of material standardization, device integration, data interoperability, and clinical translation, providing practical guidance for the rational design and deployment of next-generation multimodal SERS biosensing platforms.