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Metastatic breast cancer (MBC) remains a formidable clinical challenge due to its aggressive nature, genetic heterogeneity, and limited treatment success. Traditional pre-clinical models, including two-dimensional (2D) cell cultures and animal models, often fall short in accurately replicating the complex human tumor microenvironment (TME) and predicting clinical outcomes. This inadequacy has driven the urgent development of advanced non-animal models. This report details the capabilities of three-dimensional (3D) cell cultures, patient-derived organoids (PDOs), and organ-on-a-chip (OoC) systems as leading non-animal platforms. These innovative models offer enhanced physiological relevance, faithfully mimic tumor heterogeneity, and integrate critical TME components, providing a more reliable basis for studying the chemotherapeutic effects of drugs on breast cancer metastasis. Furthermore, the integration of emerging technologies like 3D bioprinting, CRISPR/Cas9 genome editing, advanced imaging, and artificial intelligence (AI), coupled with collaborative consortia, is poised to revolutionize personalized medicine and accelerate drug discovery, ultimately reducing reliance on animal testing and improving patient outcomes.