Fluorescence based detection is applied across various fields, including medical diagnostics and environmental sensing. A key challenge in these technologies lies in optimizing sensitivity through enhancement of the fluorescence signal. In this study, we demonstrate that combining piezoelectric and plasmonic processes increases the fluorescence yield. Piezoelectric poly­(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP), is utilized as an external electric field modulator to produce a reliable and reproducible fluorescence enhancement of InP/ZnS quantum dots approaching the single nanoparticle level. The relationship between the applied force and the fluorescence response is both experimentally quantified and theoretically modeled and the dependence of the fluorescence enhancement on the excitation wavelength and on the PVDF-HFP substrate topography is elucidated. Furthermore, fluorescence enhancement by a magnitude of order for a DNA hybridization assay on the gold-coated PVDF-HFP substrate is demonstrated, highlighting the practical applicability of this approach in biosensing.