Copyright © 2019 SPIE. Early detection of molecular targets can greatly impact the clinical diagnosis and outcome of many diseases such as cancer. Methods utilizing optical detection systems and Surface-Enhanced Raman Scattering (SERS)-labeled nanoparticles provide a way of selectively targeting and obtaining signals unique to the target diseases as well as in-vivo applications for biomass and biofuel research with plants. However, these modalities are often limited to surface level detection due to attenuation from layers of highly scattering and absorbing tissue. In this work, we utilize surface-enhanced spatially offset Raman spectroscopy (SESORS) to probe through thick tissue to overcome this limitation. This modality combines high SERS signals generated by nanoparticles with a depth resolved detection technique called spatially offset Raman spectroscopy (SORS). We show the detection and recovery of SERS signal in layered systems comprising of optically mimicking gel as well as bone material.