Breast and cervical cancers are the most common heterogeneous malignancies in women. Chemotherapy with conventional drug delivery systems having several limitations along with development of multidrug resistance compelled us to seek out targeted therapeutics. Nanoparticles are suitable substitutes to circumvent multidrug resistance for the targeted treatment of cancer. The current study was aimed to investigate the anticancer effect of carvacrol-loaded chitosan nanoparticles with topoisomerase inhibitors. The average size of carvacrol-loaded chitosan nanoparticles was found to be 80 nm with 24.7 mV ζ-potential, and maximum absorbance was observed at 275 nm. Among all drug combinations, the carvacrol nanoparticles with the doxorubicin combination group exerted greater dose-dependent growth inhibition of both MCF-7 and HeLa cells as compared to single carvacrol nanoparticles and doxorubicin. Combination index values of carvacrol nanoparticles and the doxorubicin combination group showed a strong synergistic effect as they were found to be between 0.2 and 0.4, 0.31 for MCF-7 and 0.34 for HeLa cells. The carvacrol nanoparticles in combination with doxorubicin on MCF-7 cells reduced the dose 16.32-fold for carvacrol nanoparticles and 4.09-fold for doxorubicin at 6.23 μg/mL IC, while on HeLa cells, this combination reduced the dose 13.18-fold for carvacrol nanoparticles and 3.83-fold for doxorubicin at 9.33 μg/mL IC. As the dose reduction values were greater than 1, they indicated favorable dose reduction. It was concluded that the combination of carvacrol-loaded chitosan nanoparticles with topoisomerase inhibitors may represent an innovative and promising strategy to improve the efficacy, resistance, and targeted delivery of chemotherapeutics in cancer.