Osteosarcoma (OS), the most common malignant bone tumor, remains difficult to treat, particularly in metastatic cases where outcomes are poor. Despite initial improvements with chemotherapy, therapeutic progress has stalled, largely due to the limitations of traditional two-dimensional (2D) cell cultures and animal models, which fail to capture the complexity of the tumor microenvironment (TME) and cellular heterogeneity. Recent advancements in three-dimensional (3D) culture technologies—such as spheroids, organoids, and 3D bioprinting—offer more physiologically relevant platforms for studying OS biology and for preclinical drug screening. Scaffold-free and scaffold-based spheroid models successfully replicate critical tumor features, including hypoxic gradients and extracellular matrix dynamics, while emerging organoid models retain patient-specific traits, enabling precision oncology approaches. Furthermore, 3D bioprinting techniques allow for the development of highly structured, biomimetic OS models that can better mirror the complexity of tumor. In this review, we critically assess the limitations of existing preclinical models, examine current 3D modeling approaches applied to OS research, and highlight emerging technologies that hold promise for improving disease modeling, biomarker discovery, and therapeutic development in OS.