Raman spectroscopy (RS) is a modern scientific analytic fingerprint technique that detects, examines, and analyzes the constituent chemical composition of various substances (solid–liquid–gas and plasmons) through interaction of laser light with matter. It is intelligent to present qualitative and quantitative information about the sample’s chemical composition, polymorphism, phase, crystallinity, stress/strain, and contamination and impurity/defects. The key mechanism is profoundly based on the Raman principle that was originally named after and discovered by the Indian primer scientist C.V Raman, who won the Nobel prize after the exposure of the Raman effect [Raman 1916; Krishnan 1928]. This review briefly presents the physical origin of Raman scattering explaining the key classical and quantum mechanical concepts. Molecular variations of the Raman effect will also be considered, including resonance, coherent, and enhanced Raman scattering. Further, we discuss the molecular origins of prominent bands often found in the Raman spectra of SPR (surface plasmon resonance) samples. Finally, we examine the several active variations of Raman spectroscopy techniques in practice, looking at their applications, strengths, and challenges. This review is intended to be a starting resource for scientists new to Raman spectroscopy, providing theoretical background and practical examples as the foundation for further study and exploration of SPR and surface-enhanced Raman spectroscopy (SERS) techniques. While RS is now used in biology and medicine for novel pandemic diseases, Raman spectroscopy found its first applications in physics and chemistry and was mainly used to study vibrations and structure of molecules. One early factor limiting the implementation of RS was the weak scattering signal. Large intensities of monochromatic light are required to excite a detectable signal. This requirement became much easier to realize following the invention of the laser in 1960. Over the past decades, Raman spectroscopy has been prominently exploited better in biological applications, where it is able to detect and analyze DNA and RNA molecules. Generally, there are four main types of Raman spectroscopy, but the most feasible in biological field is the SERS. The noble metal nanoclusters play an important role for nanobiomedical and modern optical devices. The present review explored the single and bi-metallic (silver (Ag), copper (Cu), silver–copper (Ag–Cu), and copper–silver (Cu–Ag)) nanoclusters embedded in soda–lime glass that is prepared by ion-exchange method. The ion-exchanged glasses are annealed by different methods (furnace and laser). These samples exhibit surface plasmon and surface enhancement effect. Optical absorption spectroscopic analysis was done on the metal nanocluster composite glasses, and the spectra are well studied as a function of various post ion-exchange treatments and different sizes. As size effects are an essential aspect of nanomaterials, the effect of size on the optical absorption metal nanoclusters was studied using theoretical models and correlated with the experimental results. Formation of embedded bi-metallic nanoclusters is also achieved by furnace annealing or laser irradiation of the sequential Cu–Ag and Ag–Cu ion-exchanged samples. The formations of core–shell structures or alloying between the metal species were confirmed from the optical absorption spectra. This review analyzes the influence of different parameters (nanocluster size, morphology, and composition as well as surface plasmon resonance (SPR) wavelength) on SERS. Experimental study of SERS substrates consists of silver, copper, and alloyed copper–silver (Cu–Ag) or silver–copper (Ag–Cu) nanoclusters of various sizes and compositions with the aim of finding the optimal conditions for fabricating substrates with maximum SERS enhancement factors. The primary aim of this work is focused on the development of novel SERS-active substrates and their applications in various research fields. The basic principle is borrowing the rough feature from the supported under layer to produce the rough noble meal surface and achieve the surface enhancement effect. The prepared substrates meet the following requirements, such as stable, reproducible, possessing large enhancement factor, and easiness for preparation. SERS opens up exciting opportunities in the field of biophysical and biomedical spectroscopy, where it provides ultrasensitive detection and characterization of biophysically/biomedically relevant molecules and processes as well as a vibrational spectroscopy with extremely high spatial resolution. This review explains many fundamental features of SERS and then describes the use of embedded nanocluster for the fabrication of highly reproducible and robust SERS substrates. The present review discusses the synthesis of single and bi-metallic nanocomposite glasses by the commercial ion-exchange technique followed by the suitable thermal treatments like furnace and laser annealing. Post treatment, the samples were subjected to various studies like optical absorption and SERS, FESEM, photoluminescence, and grazing incidence X-ray diffraction.