Invasive Mycoplasma hominis infection is a rare disease that most commonly occurs in patients after surgery, urinary catheterization, cardiopulmonary insufficiency, immunosuppression, or organ transplantation. Primary sites of infection include the skin, bone, pleural and peritoneal effusion, and the central nervous system. In a review of 65 cases of invasive infection, treatment failure occurred in 26.2% of cases. Treatment with doxycycline had a failure rate of 22.5%, while regimens without doxycycline had a failure rate of 32.0%. Prolonged antimicrobial therapy reduced the risk of failure, whereas post-transplant status increased the risk of failure approximately sixfold. The recommended therapeutic strategy is regimens containing doxycycline, especially in combination with fluoroquinolones. Increased clinical vigilance and optimized diagnostic and therapeutic approaches are important to reduce treatment failure rates.