Surface-Enhanced Raman Scattering (SERS) is a highly sensitive, nondestructive analytical technique that leverages plasmonic enhancement to detect molecular vibrational fingerprints at ultralow concentrations. This chapter explores the development and application of paper-based SERS substrates, an emerging class of cost-effective, flexible, and eco-friendly platforms. Leveraging cellulose’s unique properties, such as porosity, biodegradability, and hydrophilicity, these substrates offer significant advantages over traditional rigid materials like glass or silicon. We discuss the principles of SERS enhancement, the design and preparation of paper-based substrates, their characterization, and their diverse applications in fields such as biomedical diagnostics, food safety, and environmental monitoring. Challenges, including nanoparticle uniformity and substrate durability, are addressed alongside future perspectives for advancing this technology.