The ability of nano secondary ion mass spectrometry (NanoSIMS) to locate and analyze Raman active gold core nanoparticles (R-AuNPs) in a biological system is compared with the standard analysis using the scanning electron microscope (SEM). The same cell with R-AuNPs on and inside the macrophage was analyzed with both techniques to directly compare them. SEM analysis showed a large number of nanoparticles within the cell. Subsequent NanoSIMS analysis showed fewer R-AuNPs with lower spatial resolution. SEM was determined to be superior to NanoSIMS for the analysis of inorganic nanoparticles in complex biological systems.