Purpose of Review <p>Myosteatosis, defined as the pathological accumulation of fat within skeletal muscle, has emerged as a critical yet underrecognized feature of muscle aging and metabolic dysregulation. Despite its growing clinical relevance, the field remains constrained by fragmented definitions, heterogeneous diagnostic criteria, and limited mechanistic understanding, all of which hamper effective detection and intervention. This review synthesizes current evidence to delineate the epidemiological landscape and clinical ramifications of myosteatosis across organ systems, and to highlight emerging myokine-driven endocrine signaling, biomarker candidates, and diagnostic strategies.</p> Recent Findings <p>Population-level studies increasingly implicate myosteatosis in impaired mobility, heightened morbidity, and poor survival in chronic disease contexts. Susceptibility is influenced by age, sex, ethnicity, and genetic background, while pathological integration with sarcopenia, cardiometabolic dysfunction, malignancy, and systemic frailty is becoming evident. Additionally, dysregulated myokine-mediated endocrine signaling and altered muscle-adipose crosstalk are increasingly recognized as adjunct pathological signatures of myosteatosis, with potential relevance to its progression and metabolic complications. Advances in diagnostic strategies, including quantitative imaging modalities and circulating biomarkers, alongside ongoing progress toward laboratory determinants and assay standardization, have begun to refine disease characterization and translational potential, though consensus remains limited.</p> Summary <p>Myosteatosis is a modifiable disease trait that bridges muscle quality decline with systemic metabolic risk. By outlining unresolved challenges and future research priorities, this review aims to reframe myosteatosis as a targetable axis in precision medicine, with implications for risk stratification, therapeutic development, and improved clinical outcomes.</p>