Femoral head necrosis (FHN) is a progressive and disabling disorder caused by reduced blood supply to the femoral head. Current treatments focus mainly on slowing progression, but often fail to reverse necrosis at an early stage or reliably prevent disease progression. Most approaches lack precise molecular targets for early intervention. Ozone therapy represents a potential option due to pleiotropic biological effects such as modulation of oxidative stress, improvement of microcirculation and anti-inflammatory activity. However, the mechanisms of ozone therapy remain poorly understood. Clinical evidence is limited and inconsistent, while the absence of standardized protocols hinders its evidence-based implementation. The article proposes biomarkers as a translational bridge linking ozone-induced biological responses to FHN pathology. It further outlines a dynamic biomarker-driven framework that will allow ozone therapy to evolve from an empirical intervention into a mechanism-informed, personalized, and standardized precision strategy.