The present study introduces a high-efficiency nanocomposite material featuring a zinc-based metal–organic framework and a novel porous activated carbon derived from bread waste. The prepared nanocomposite, namely Zn-MOF-5@BHPAC, has been synthesized by a low-temperature hydrothermal process and coated onto the surface of a stainless steel wire with epoxy glue. The fabricated fiber has been employed as an SPME fiber applied in the extraction and pre-concentration of some nonsteroidal anti-inflammatory drugs (NSAIDs) before their high-performance liquid chromatography-ultraviolet (HPLC-UV) studies. The characterization studies were performed utilizing field emission scanning electron microscopy, elemental mapping, energy-dispersive X-ray spectroscopy, elemental analyzer, Fourier-transform infrared spectroscopy, and Brunauer–Emmett–Teller surface area analysis. Under the optimal conditions, the method demonstrated low detection limits (LODs, 0.06–0.15 µg L–1), wide linear ranges (LRs, 0.20–380 µg L–1) with good linearity (R2 > 0.991), good precisions (RSDs < 6.95%), and acceptable relative recoveries (RR > 85%). Using the green and affordable biomass of bread as a novel carbon-rich source is an innovative idea provided in this study. In addition, the hybridization of the obtained carbon-based material with the MOF compound to create a new high-capacity sorbent is another strength of the proposed method. Long service lifetime, economic efficiency, environmental friendliness, and high extraction capability were some of the other advantages of the suggested procedure. Therefore, the method can utilize successfully for the simultaneous determination of NSAIDs (as model analytes) in different matrixes.