Background: Drug-tolerant persister cells (DTPs) are key culprits for cancer relapse. By shifting from proliferative to a dormant state, DTPs tolerate conventional chemotherapy. To sustain this state, DTPs rely on mitochondrial respiratory chain, necessitating aldehyde dehydrogenase (ALDH) upregulation to detoxify toxic byproducts. This study aims to exploit this dependency by using disulfiram, an ALDH inhibitor, to induce aldehyde accumulation and subsequent apoptosis. Here, we developed EGFR-targeted nanoparticles to deliver disulfiram and docetaxel and evaluated their physicochemical properties. Methods: Docetaxel and disulfiram were each encapsulated in PLGA nanoparticles via solvent evaporation method. Conjugation of nanoparticles with cetuximab was performed using EDC/NHS chemistry. Results: DLS analysis showed that docetaxel- and disulfiram-encapsulated nanoparticles had sizes of 148.5 ± 4.8 nm and 149.3 ± 1.0 nm, PDIs of 0.238 ± 0.02 and 0.140 ± 0.07, and zeta potentials of –29.2 ± 0.9 mV and –30.3 ± 1.0 mV, respectively. Loading capacity and encapsulation efficiency were 2.0 ± 0.02% and 20.04 ± 0.2% for docetaxel, and 2.6 ± 0.2% and 41.43 ± 3.1% for disulfiram. The conjugation efficiency with cetuximab was 31.6 ± 0.6%. Conclusion: We successfully formulated EGFR-targeted nanoparticles co-delivering disulfiram and docetaxel. This platform could be proposed as a potential candidate for eliminating DTPs and overcoming chemotherapy resistance.