AbstractDrug delivery systems (DDSs) are designed to deliver therapeutic agents to specific target sites while minimizing systemic toxicity. Recent developments in drug‐loaded DDSs have demonstrated promising characteristics and paved new pathways for cancer treatment. Light, a prevalent external stimulus, is widely utilized to trigger drug release. However, conventional light sources primarily concentrate on the ultraviolet (UV) and visible light regions, which suffer from limited biological tissue penetration. This limitation hinders applications for deep‐tissue tumor drug release. Given their deep tissue penetration and well‐established application technology, X‐rays have recently received attention for the pursuit of controlled drug release. With precise spatiotemporal and dosage controllability, X‐rays stand as an ideal stimulus for achieving controlled drug release in deep‐tissue cancer therapy. This article explores the recent advancements in using X‐rays for stimulus‐triggered drug release in DDSs and delves into their action mechanisms.