Despite significant advancements in cardiovascular interventions, managing treatment-resistant cardiac arrhythmias and in-stent restenosis (ISR) remains challenging. Hypofractionated radio-ablative techniques, such as high-dose stereotactic body radiotherapy (SBRT), have shown promise in noninvasively targeting ventricular arrhythmias in patients unresponsive to medications or radiofrequency (RF) ablation. These arrhythmias are often due to aberrant ventricular conduction channels that can be fatal if left untreated. In parallel, ISR continues to pose difficulties, particularly in cases involving complex or multilayer drug-eluting stents (DES). While DES has reduced restenosis rates, recurrence still occurs. Intravascular brachytherapy (IVBT), once effective during the bare-metal stent era, is being reconsidered as a treatment option for recurrent DES ISR, especially in challenging multilayer scenarios. Together, these emerging radiotherapeutic strategies reflect a broader shift toward noninvasive solutions in cardiovascular disease management.