Hypoxia is a fundamental hallmark of cancer and a central architect of the tumor microenvironment, influencing virtually every stage of tumor initiation, progression, metastasis, and therapeutic response. Oxygen deprivation stabilizes key transcriptional regulators such as HIF-1α and HIF-2α, driving extensive molecular reprogramming across malignant, stromal, vascular, and immune compartments. Through dynamic interactions with metabolic stress, acidosis, extracellular matrix remodeling, inflammatory signaling, and mechanical forces, hypoxia generates spatially and temporally heterogeneous niches that shape tumor evolution and clinical outcomes across cancer types.

Despite major progress in research in this field, significant challenges remain. The intrinsic heterogeneity and plasticity of hypoxic regions complicate precise measurement, modeling, and therapeutic targeting. Integrating multi-scale data—from molecular circuits and single-cell states to tissue architecture and systemic influences—remains a pressing need. Translational gaps persist between experimental models and patient tumors, and robust biomarkers that reliably capture hypoxia-driven vulnerabilities are still under development. Moreover, resistance mechanisms emerging under hypoxic pressure continue to limit the durability of current therapies.

This Collection aims to provide a comprehensive, multidisciplinary platform encompassing original research articles, methodological advances, and reviews that collectively address fundamental mechanisms, technological innovations, translational strategies, and clinical implications of hypoxia within tumor ecosystems.

By fostering cross-disciplinary integration and bridging experimental and clinical topics, this collection will serve as a definitive resource for researchers and clinicians, accelerate conceptual advances, and stimulate innovative therapeutic approaches targeting hypoxia and the tumor microenvironment.