<p>Cardiovascular diseases remain the leading global cause of death and disability, prompting the need for precise mapping of molecular drivers that couple ionic flux to signaling. Because of its regulatory role in ionic balance and signaling, transient receptor potential melastatin 7 (TRPM7) channel-kinase has emerged as a key molecular determinant of cardiovascular physiology and pathophysiology. Following an overview of Ca²⁺ signaling in cardiovascular biology, we summarize current knowledge of TRPM7 from its structure to its function, including channel architecture, gating properties, and kinase regulation by metabolic and redox signals with a diverse substrate repertoire. Integration of evidence across cardiovascular systems biology shows that TRPM7 acts in a context-dependent manner. In the vasculature, TRPM7 shapes endothelial function, smooth muscle phenotype and remodeling, and participates in neurogenic control of blood pressure through carotid body glomus cells. In the heart, TRPM7 regulates pacemaking and conduction through transcription control of ion channel genes, contributes to atrial fibrogenesis via Ca²⁺-dependent fibroblast activation, and worsens ischemia-reperfusion injury through ionic overload and inflammasome signaling. In metabolic heart disease, TRPM7 kinase activity links mitochondrial oxidative stress to diastolic dysfunction, suggesting relevance to heart failure with preserved ejection fraction (HFpEF). Finally, we appraise pharmacological tools that target TRPM7, including natural and synthetic channel and kinase modulators, and outline translational considerations for organ- and disease-specific modulation. Overall, TRPM7 is a central integrator of ionic homeostasis and kinase signaling in cardiovascular biology and represents a promising, yet nuanced, therapeutic target that requires context-aware strategies.</p>