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Although the therapeutic armamentarium for brain metastases (BMs) has been expanded from innovative surgical techniques and radiotherapy to include targeted therapies and immunotherapy, the prognosis of BMs remains poor. Despite the proven efficacy of numerous compounds in preclinical studies, the limited penetration of promising therapeutic agents across the blood-brain barrier (BBB) remains an unaddressed issue. Recently, low-intensity magnetic resonance–guided focused ultrasound (MRgFUS) in combination with microbubbles has been shown to overcome vascular and cellular transport barriers in the brain and tumor microenvironment, resulting in increased drug diffusion and preliminary effective results. Preclinical studies have investigated the increased penetration of many therapeutic agents including doxorubicin, trastuzumab, and ipilimumab into the CNS with promising results. Furthermore …