Radiation-induced heart disease (RIHD) is a prevalent cardiovascular complication of radiation therapy, with coronary heart disease being the most common manifestation. Clinical presentations of RIHD vary and may include conduction abnormalities, ischemic heart disease, cardiomyopathy, heart failure, and valvular damage. Even low doses of radiation significantly increase the risk of cardiovascular disease, often associated with severe stenosis detected via angiography. Radiation-induced damage to the cardiac endothelium triggers inflammatory responses and oxidative stress, which contribute to the progression of atherosclerosis. This study explores how radiation activates multiple signaling pathways through the generation of reactive oxygen species, resulting in vascular endothelial damage, cellular senescence, inflammatory responses, and DNA damage. It further examines the impact of radiation on vascular integrity and tight junction proteins, leading to increased vascular permeability and infiltration by inflammatory cells. From a clinical perspective, we emphasize the challenges posed by the coexistence of tumors in many patients with RIHD, as tumors complicate the microenvironment and may have mutually reinforcing interactions with radiation-induced damage. We also discuss various therapeutic strategies, including novel approaches targeting cellular senescence and immune responses, with a focus on the potential use of navitoclax and IL-6 (interleukin-6) inhibitors to prevent irreversible cardiomyocyte fibrosis and ongoing vascular damage. In conclusion, RIHD is a multifaceted disease involving complex biological processes and signaling pathways. Early intervention and targeted therapies are crucial for improving patient outcomes. Future research should prioritize uncovering the molecular mechanisms of RIHD and developing more effective therapeutic strategies.