Deciphering Cancer Therapy-Induced Cardiotoxicity in the Era of Spatial and Multi-Omics from Systemic Mechanisms to <i>In Situ</i> Microenvironments

Cardio-oncology has emerged as a critical discipline addressing the cardiovascular sequelae of antineoplastic therapies. While traditional chemotherapy, targeted therapies, and immune checkpoint inhibitors (ICIs) have revolutionized cancer survival, they are frequently accompanied by cardiotoxicity ranging from asymptomatic left ventricular dysfunction to fulminant myocarditis. Current clinical strategies, relying heavily on echocardiography and serum biomarkers, often fail to detect early molecular perturbations or elucidate the complex multicellular interactions within the cardiac microenvironment. The advent of multi-omics technologies, genomics, transcriptomics, proteomics, and metabolomics, has provided systemic insights into these pathomechanisms. More recently, the integration of single-cell RNA sequencing (scRNA-seq) and spatial omics has enabled "<i>in situ</i>" visualization of cellular heterogeneity and intercellular communication, resolving the "blind spots" of bulk sequencing. This review synthesizes the current landscape of therapy-induced cardiotoxicity, highlights the limitations of conventional methodologies, and comprehensively examines how multi-dimensional omics strategies are reshaping our understanding of mechanisms, biomarker discovery, and precision cardioprotection.