Space oncology is an emerging discipline that leverages the unique space environment—including high-Z and high-energy (HZE) particle radiation, microgravity, and their combined effects—to investigate the fundamental and translational aspects of cancer initiation, progression, diagnosis, and therapy. This review presents the research background and scientific significance of space oncology and systematically summarizes major domestic and international research initiatives and recent progress. Special emphasis is placed on two core directions: carcinogenesis of normal cells and proliferation inhibition/death of cancer cells under space radiation conditions. The underlying mechanisms are discussed, including DNA damage repair, non-coding RNA regulation, cytoskeletal dynamics, organelle crosstalk (e.g., mitochondria), and microenvironment remodeling. Key scientific challenges currently facing the field include the unclear dose-response relationship between cancer risk and the different qualities of space radiation, unvalidated molecular mechanisms of tumor suppression, and poorly understood differences in individual radiosensitivity. With the completion of the China Space Station and the establishment of ground-based simulation platforms, China has unique infrastructure and collaborative network advantages. To advance the field, five major scientific questions should be systematically addressed: dose-response relationships, carcinogenic mechanisms, individual susceptibility, stress response and death of cancer cells, and tumor microenvironment regulation. A three-phase roadmap is proposed: short-term to build databases and collaborative networks, medium-term to expand cancer types and promote clinical translation, and long-term to establish a theoretical framework and support deep-space health. The ultimate goal is to develop a comprehensive theoretical system for space oncology, thereby providing novel strategies for human health protection and for cancer prevention, diagnosis, and treatment on Earth.