Over the past few decades, breakthroughs in cancer biology at the molecular level have revolutionised cancer treatment. Enhanced precision in radiotherapy has not only reduced patient side-effects, but also enabled the delivery of high-dose stereotactic extracranial irradiation with unprecedented accuracy. Simultaneously, the number of medical therapies available for clinical care continues to grow. Despite the progress made with combined chemoradiotherapy, only a few drug–radiotherapy combinations have received clinical approval, leaving a vast landscape of untapped opportunities for basic, translational, and clinical research, particularly in early-phase drug–radiotherapy trials.