Adipose-derived mesenchymal stem cells (ADSCs) have emerged as promising seed cells for bone tissue repair in regenerative medicine, owing to their distinct advantages including abundant sources, minimally invasive isolation, low immunogenicity, and multidirectional differentiation potential. The directional homing of ADSCs to the medullary cavity represents a core prerequisite for their therapeutic efficacy in bone regeneration. However, the specific regulatory details underlying this homing process remain poorly elucidated, which poses a critical bottleneck restricting their clinical translation. Focusing on the unique microenvironment of the medullary cavity, this review systematically summarizes the exclusive molecular mechanisms governing ADSCs homing to the medullary cavity, clarifies the bone marrow-targeted guidance characteristics of chemokine signaling axes, the patterns of integrin-mediated transendothelial migration across bone marrow vascular endothelium, as well as the synergistic regulatory network of intracellular signaling pathways. It further analyzes the specific effects of intrinsic cellular properties, medullary cavity microenvironment, and exogenous interventions on homing efficiency, and elucidates the bone marrow-specific mechanisms by which ADSCs promote bone tissue repair after successful homing. This review aims to provide a targeted theoretical basis and research insights for optimizing the medullary cavity homing efficiency of ADSCs and facilitating their clinical translation in the field of bone repair.