Owing to drawbacks in the current common cancer therapies including surgery, chemotherapy and radiotherapy, the development of more reliable, low toxic, cost-effective and specific approaches such as immunotherapy is crucial. Breast cancer is among the leading causes of morbidity and mortality with a developed anticancer resistance. Accordingly, we attempted to uncover the efficacy of metallic nanoparticles (MNPs)-based breast cancer immunotherapy emphasizing trained immunity provocation or innate immunity adaptation. Due to the immunosuppressive nature of the tumor microenvironment (TME) and the poor infiltration of immune cells, the potentiation of an immune response or direct combat is a goal employing NPs as a burgeoning field. During the recent decades, the adaptation of the innate immunity responses against infectious diseases and cancer has been recognized. Although the data is in a scarcity with regard to a trained immunity function in breast cancer cells’ elimination, this study introduced the potential of this arm of immunity adaptation using MNPs.