Abstract: Staphylococcus aureus is a facultative intracellular bacterium capable of establishing an intracellular infection niche through various mechanisms, including phagosome escape, survival in phagolysosomes and interference with or exploitation of host autophagy. It thereby evades antimicrobial drug killing and immune-mediated clearance, ultimately leading to various severe infectious diseases. Due to the difficulty of traditional antimicrobial agents, antimicrobial peptides and bacteriophages effectively entering cells, the complete eradication of intracellular S. aureus has become a serious challenge in clinical treatment. Against this backdrop, nanocarriers, as an emerging drug delivery platform, can achieve precise targeting and efficient delivery of antimicrobial drugs to infected cells through functional modification, thus potentially eradicating intracellular bacteria. This article reviews the mechanisms of S. aureus entry into cells, its intracellular survival and promising drug delivery systems for combating intracellular bacteria, aiming to provide a theoretical foundation for the development of effective strategies to eradicate intracellular S. aureus.