Raman spectroscopy fingerprinting features many technological applications. For this purpose, the weak Raman signals need to be boosted dramatically by surface-enhanced Raman spectroscopy (SERS), which provides immense Raman enhancement via plasmonic and chemical mechanisms (CM). In this manuscript, we reveal the giant chemical as well as extremely high SERS enhancement from a three-dimensional MoS2-x O x -gold nanoparticle (GNP) hybrid, which has capability for ultrasensitive label-free sensing of chemical and biological molecules. Notably, reported data show that the chemical enhancement for the MoS2-x O x surface is ∼105, which is comparable with the plasmonic enhancement factor (EF) by GNP. Reported data show that the total Raman EF is ∼1013 from the GNP-MoS2-x O x hybrid. Intriguingly, combined experimental and theoretical finite difference time domain stimulation modeling findings show that the synergistic effect of electromagnetic mechanism and CM is responsible for huge SERS enhancement. Experimental results demonstrate that a proposed hybrid SERS platform can be used for fingerprint sensing of different multiple drug resistance bacteria at 5 cfu/mL concentration. Importantly, the current manuscript provides a good strategy for manipulating the SERS sensitivity to 13 orders of magnitude, which is instrumental for next-generation technological applications of Raman spectroscopy.