The efficacy of a single clinical nanodrug for cancer treatment is still unsatisfactory, especially for drug-resistant cancer. Herein, we applied a fasting-mimicking diet (FMD) approach via dietary intervention to assist single clinical nanodrug for breast or ovarian cancer treatments instead of using multi-drug therapies which might cause adverse side effects. Specifically, we adopted Doxil or Abraxane to treat human breast tumor-bearing nude mice and Doxil to treat the human ovarian tumor and drug-resistant ovarian tumor-bearing nude mice under FMD conditions, respectively. According to the results, the FMD condition can promote the cellular uptake and cytotoxicity of a single nanodrug, reduce the ATP level in drug-resistant tumor cells to hinder drug efflux, normalize tumor blood vessels, relieve tumor hypoxia, and increase the accumulation of nanodrugs at tumor sites, thereby enhancing the therapeutic effects on these types of human cancers. Collectively, these results demonstrate that the FMD strategy of significance can become a practical, alternative, and promising assistant for single nanodrug for enhancing cancer therapy and clinical translation.