Recently, we described a new technique, targeted plasmonically enhanced single cell imaging spectroscopy (T-PESCIS), which exploits the plasmonic properties of gold nanoparticles, e.g. gold nanospheres, to simultaneously obtain enhanced intracellular Raman molecular spectra and enhanced Rayleigh cell scattering images throughout the entire span of a single cell cycle. In the present work, we demonstrate the use of T-PESCIS in evaluating the relative efficacy and dynamics of two popular chemotherapy drugs on human oral squamous carcinoma (HSC-3) cells. T-PESCIS revealed three plasmonically enhanced Raman scattering vibration bands, 500, 1000, and 1585 cm(-1), associated with the cellular death dynamics. Detailed analysis indicated that the decrease in the 500 cm(-1) band did not correlate well with drug efficacy but could indicate death initiation. The time it takes for the relative intensity of either the 1000 or 1585 cm(-1) band ("SERS death" bands) to appear and increase to its maximum value after the injection of a known concentration of the drug can be related to the drug's efficacy. The inverse ratio, termed cell death enhancement factor, of these characteristic death times when using either band, especially the spectrally sharp band at 1000 cm(-1), gave the correct drug efficacy ratio as determined by the commonly used XTT cell viability assay method. These results strongly suggest the potential future use of this technique in determining the efficacy, dynamics, and molecular mechanisms of various drugs against different diseases.