This study developed transferrin-PEGylated docetaxel albumin nanoparticles (Tf-PEG-DANPs)-loaded lipid microbubbles and characterized their properties. Combined with ultrasound-targeted microbubble destruction (UTMD) technology, the drug targeting ability, therapeutic efficacy, toxicity, and adverse effects were systematically investigated through in vitro cellular experiments and in vivo animal models. The results demonstrated that Tf-PEG-DANPs-loaded lipid microbubbles exhibited a particle size of (152.11±16.28) nm with a ζ potential of (–6.24±2.35)mV, and displayed uniform quasi-spherical morphology. The encapsulation efficiency and drug loading were (94.61±0.67)% and (8.82±0.92)%, respectively. Compared with the conventional formulations, the Tf-PEG-DANPs-loaded lipid microbubbles combined with UTMD significantly inhibited proliferation and induced apoptosis in mouse 4T1 breast cancer cells. Furthermore, in vivo pharmacodynamic evaluationsshowed enhanced tumor suppression efficacy without inducing hepatic or renal toxicity in murine models. This research provided a novel targeted therapeutic strategy with high efficacy and low systemic toxicity, demonstrating substantial clinical potential for breast cancer treatment.