Motivated by the desire for more sensitivity and stable surface-enhanced Raman scattering (SERS) substrates to trace detect chloramphenicol due to its high toxicity and ubiquity, MXene has attracted increasing attention and is encountering the high-priority task of further observably improving detection sensitivity. Herein, a universal SERS optimization strategy that incorporates NH4VO3 to induce few-layer MXenes assembling into multiporous nanosheet stacking structures was innovatively proposed. The synthesized Nb2C-based multiporous nanosheet stacking structure can achieve a low limit of detection of 10-10 M and a high enhancement factor of 2.6 × 109 for MeB molecules, whose detection sensitivity is improved by 3 orders of magnitude relative to few-layer Nb2C MXenes. Such remarkably enhanced SERS sensitivity mainly originates from the multiple synergistic contributions of the developed physical adsorption, the chemical enhancement, and the conspicuously improved electromagnetic enhancement arising from the intersecting MXenes. Furthermore, the improved SERS sensitivity endows Nb2C-based multiporous structures with the capability to achieve ultrasensitive detection of chloramphenicol with a wide linear range from 100 μg/mL to 1 ng/mL. We believe it is of great significance in conspicuously developing the SERS sensitivity of other MXenes with surficial negative charges and has a great promising perspective for the trace detection of other antibiotics in microsystems.