The dependence of colloidal stability, particle aggregation and SERS reproducibility on the molecular nature of RRs represents one of the main drawbacks in the development of Raman tags based on AuNPs. As a matter of fact, variations in RRs structure affects their density at the NP surface, as well as the NP dispersibility and stability against degradation. For this reason, often SERS probes need specific design for the selected RR, and changes in the RR require significant adjustments of synthetic protocols and conditions. For instance, in the case of AuNP clusters, slight variations in the chemical structure of RR can lead to uncontrolled aggregation due to changes in steric and electrostatic energy contributions. All these hurdles can be circumvented by the presented approach, by encapsulating RRs in the lipid bilayer, thus avoiding effects on the SERS probe colloidal stability and, at the same time, ensuring the effective shielding of the RR from the environment, preserving its optical features.