Cardiovascular disease is a major global health burden, responsible for nearly 40% of all deaths, with chronic heart failure being a critical stage. Despite advancements, survival rates for chronic heart failure remain low, with significant financial and health impacts. Innovations in genetic tools have enhanced understanding of signaling pathways involved in heart failure, though translation into clinical practice is still limited. Current treatments include beta-blockers, aldosterone antagonists, and angiotensin inhibitors, with newer drugs like sacubitril/valsartan and sodium-glucose cotransporter 2 inhibitors showing promise. This review discusses cardiovascular biomaterials (CB), categorized into metals, polymers, and biological materials. Blood compatibility is a key challenge, with surface modification techniques improving compatibility. Induced pluripotent stem cells, endothelialization of cardiac implants, and current CB trends are highlighted. The review also covers key signaling pathways in heart failure, including calcineurin-NFAT, G protein-coupled receptor, ERK, p38, PI3K, Wnt, and others. These pathways are crucial for understanding and treating heart failure, with miRNAs, lncRNAs, and other regulatory molecules playing significant roles. Gene therapy, including plasmid-based, viral-based, and oligonucleotide-based methods, is explored for its potential in treating cardiovascular diseases. Stem cell therapy, while promising, faces challenges such as limited integration with cardiomyocytes. Biological materials, like porcine and bovine valves, are used in valve replacement, though calcification remains a concern. Naturally derived biomaterials, including chitosan, collagen, and fibrin, are effective for tissue engineering, while synthetic materials offer mechanical stability and tunability. Composite scaffolds combining natural and synthetic components are increasingly used for their mechanical and biological properties. 3D printing and bioprinting enable the creation of patient-specific models and scaffolds, while electrospinning produces nano- and micrometer-scale fibers for tissue engineering. These advancements highlight the importance of interdisciplinary research in developing effective cardiovascular treatments.Cardiovascular disease is a major global health burden, responsible for nearly 40% of all deaths, with chronic heart failure being a critical stage. Despite advancements, survival rates for chronic heart failure remain low, with significant financial and health impacts. Innovations in genetic tools have enhanced understanding of signaling pathways involved in heart failure, though translation into clinical practice is still limited. Current treatments include beta-blockers, aldosterone antagonists, and angiotensin inhibitors, with newer drugs like sacubitril/valsartan and sodium-glucose cotransporter 2 inhibitors showing promise. This review discusses cardiovascular biomaterials (CB), categorized into metals, polymers, and biological materials. Blood compatibility is a key challenge, with surface modification techniques improving compatibility. Induced pluripotent stem cells, endothelialization of cardiac implants, and current CB trends are highlighted. The review also covers key signaling pathways in heart failure, including calcineurin-NFAT, G protein-coupled receptor, ERK, p38, PI3K, Wnt, and others. These pathways are crucial for understanding and treating heart failure, with miRNAs, lncRNAs, and other regulatory molecules playing significant roles. Gene therapy, including plasmid-based, viral-based, and oligonucleotide-based methods, is explored for its potential in treating cardiovascular diseases. Stem cell therapy, while promising, faces challenges such as limited integration with cardiomyocytes. Biological materials, like porcine and bovine valves, are used in valve replacement, though calcification remains a concern. Naturally derived biomaterials, including chitosan, collagen, and fibrin, are effective for tissue engineering, while synthetic materials offer mechanical stability and tunability. Composite scaffolds combining natural and synthetic components are increasingly used for their mechanical and biological properties. 3D printing and bioprinting enable the creation of patient-specific models and scaffolds, while electrospinning produces nano- and micrometer-scale fibers for tissue engineering. These advancements highlight the importance of interdisciplinary research in developing effective cardiovascular treatments.