nsPEFs constitute a temporally sharp physical perturbation, independent of sustained chemical input, for probing the impact on intracellular state. In PC-12 cells, nsPEFs induce neuritogenesis, enhanced neurite outgrowth when NGF-treated, increased C–H Raman scattering intensity, cell volume contraction, and intracellular heating. The research question posed here concerns the existence of a relationship between the early nsPEF-induced changes observable by Raman spectroscopy and the subsequent neuronal commitment of the treated cell population. A novel definition of the Biophysical Commitment Index (BCI), based on cytoplasmic crowding effects, cell-area shrinkage, thermal dynamics of the intracellular medium, and nsPEF{}-waveform-related parameters, serves as a physiologically motivated predictor of nsPEF-induced neuronal commitment. Herein, the BCI{} predictor is determined by hierarchical modeling, mediated by Raman-observables and bright-field morphometrics of the individual cells nested within biological replicates, in a way consistent with leave-one-dish-out cross-validation. Contributions of this work include the development of a physically intuitive model relating nsPEF-triggered C–H and O–H vibrations to further neuronal commitment; a validation scheme that accounts for the nested structure of experimental data and preserves the distinction between treatment assignment and early intracellular state; and an experimental design for assessing label-free Raman spectroscopy as a biomarker of drug-free neuronal differentiation.