Raman spectroscopy has risen with the current trends for detection biomedical interest analytes, as it offers unmatched molecular selectivity, minimal sample preparation, and non-destructive analysis. Moreover, the unparalleled performance of this technique is found in surface-enhanced Raman scattering (SERS), a technique that drastically boosts Raman signals, enabling the detection of analytes down to the single-molecule and even in the most complex biological environments. Despite its great potential, there have been several drawbacks faced, demanding a new class of SERS substrates with elevated stability, reproducibuility and designed to maximize light-matter interactions to achieve clean signals. In order to overcome this, an in-situ synthesis of gold nanoparticles with controlled morphology, immobilized in plasmonic platforms that collapse on demand to increase the number of ‘hotspots’ is proposed. Pushing the boundaries further, the use of anisotropic gold nanostructures, crafted via a green, one-pot synthesis in deep eutectic solvents (DES) and anchored by cellulose nanocrystals (CNCs), signals a shift toward sustainable, high-performance SERS materials. Together, these innovations chart an exciting new course for the ultra-sensitive, eco-conscious detection of biomedical analytes.