Purpose: The goal of this work is to investigate the anticancer potency of magnetically induced muscle secretome on breast cancer in vitro, in vivo and ex vitro. The work also examines the function of magnetically mediated preconditioning paradigm to enhance muscle secretome release and production. Briefly (10 min) exposing C2C12 myotubes to low amplitude (1.5 milliTesla) pulsed electromagnetic fields (PEMFs) generated a conditioned media (pCM) that mitigated breast cancer cell growth, migration and invasiveness in vitro, whereas the conditioned media harvested from unexposed myotubes, representing constitutively released secretome (cCM), was less effective. Ex vivo, administering pCM to breast cancer microtumors engrafted onto the chorioallantoic membrane of the chicken egg reduced tumor volume and vascularity. In vivo, blood serum collected from PEMF-exposed or exercised mice allayed breast cancer cell growth, migration and invasiveness. Based on PEMF-induction of the muscle secretome, a preconditioning methodology was developed to enhance secretome production and release. HTRA1 (High-Temperature Requirement A Serine Peptidase 1) was upregulated in the pCM and was shown necessary for myogenic progression and anticancer potency. HTRA1 expression hence embodied key adaptive features of the pCM preconditioning paradigm and emulating an exercise-like effect. Brief and non-invasive PEMF stimulation may represent a method to commandeer the secretome response of muscle for clinical exploitation in cancer. Brief and non-invasive pulsed electromagnetic field (PEMF) stimulation was shown to induce the secretome response of muscles akin to exercise to impact cancer viability and epithelial-mesenchymal transition (EMT). Moreover, the preconditioning of cells to PEMF may represent a method to induce the secretome response of muscles for clinical exploitation in cancer.