Chronic liver inflammation, a pervasive global health issue, results in millions of annual deaths due to its progression from fibrosis to the more severe forms of cirrhosis and hepatocellular carcinoma (HCC). This insidious condition stems from diverse factors such as obesity, genetic conditions, alcohol abuse, viral infections, autoimmune diseases, and toxic accumulation, manifesting as chronic liver diseases (CLDs) such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease (ALD), viral hepatitis, drug-induced liver injury, and autoimmune hepatitis. Late detection of CLDs necessitates effective treatments to inhibit and potentially reverse disease progression. However, current therapies exhibit limitations in consistency and safety. A potential breakthrough lies in nanoparticle-based drug delivery strategies, offering targeted delivery to specific liver cell types, such as hepatocytes, Kupffer cells, and hepatic stellate cells. This review explores molecular targets for CLD treatment, ongoing clinical trials, recent advances in nanoparticle-based drug delivery, and the future outlook of this research field. Early intervention is crucial for chronic liver disease. Having a comprehensive understanding of current treatments, molecular biomarkers and novel nanoparticle-based drug delivery strategies can have enormous impact in guiding future strategies for the prevention and treatment of CLDs.