Tip-enhanced resonance couplings (TERCs) are experimentally revealed by high vacuum tip-enhanced Raman spectroscopy (HV-TERS) and theoretically interpreted. The Fermi resonance and Darling–Dennison resonance are successfully observed in HV-TERS, which are the first overtone (or combinational mode)-fundamental interaction (2:1 resonance coupling) and the first overtone-first overtone resonant interaction (1:1 resonance coupling), respectively. The electric field gradient plays an important role on TERCs in HV-TERS at the level of the second-order perturbation theory. The molecular tautomeric effects are also observed from thiourea adsorbed on Ag film in HV-TERS. The reported HERCs can provide a deeper understanding of the importance of molecular anharmonicity in high-order perturbation for TERS. HV-TER spectra provide ‘additional’ nonlinear Raman peaks, compared with the harmonic zero-order perturbation in HV-TERS, and thus enable ultrasensitive chemical analysis at the nanoscale with more vibrational information.