Simple SummaryBreast cancer that spreads to other parts of the body, known as metastatic breast cancer, is a serious and life-threatening condition, leading to decreased survival. Current treatment options for metastatic breast cancer are similar to those used for the initial cancer, including surgery, chemotherapy, immunotherapy, and radiotherapy. However, metastatic breast cancer is more complicated because cancer cells in different organs behave differently, making it harder to treat effectively. To address this challenge, nanotechnology in combination with current cancer therapies can be used. Nanotherapeutics involves using tiny particles to deliver therapies directly to cancer cells. This approach has shown promise in both primary and metastatic breast cancer treatments, with new ideas and technologies constantly being developed. This review article provides detailed information about the recent progress and future possibilities of using nanotherapeutics specifically for the treatment of metastatic breast cancer. It takes into account the unique characteristics of the disease, as well as discusses how nanotechnology can be combined with existing treatments. It also explores the potential for these combined approaches to be used in future clinical settings.AbstractMetastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed by combining current cancer therapies with nanotechnology. The applications of nanotherapeutics for both primary and metastatic BC treatments are developing rapidly, and new ideas and technologies are being discovered. Several recent reviews covered the advancement of nanotherapeutics for primary BC, while also discussing certain aspects of treatments for metastatic BC. This review provides comprehensive details on the recent advancement and future prospects of nanotherapeutics designed for metastatic BC treatment, in the context of the pathological state of the disease. Furthermore, possible combinations of current treatment with nanotechnology are discussed, and their potential for future transitions in clinical settings is explored.