Cardiovascular diseases are the leading causes of death worldwide. However, there are still shortcomings in the currently employed treatment methods for these diseases. Therefore, exploring the molecular mechanisms underlying cardiovascular diseases is an important avenue for developing new treatment strategies. Previous studies have confirmed that metabolic and epigenetic alterations are often involved in cardiovascular diseases across patients. Moreover, metabolic and epigenetic factors interact with each other and affect the progression of cardiovascular diseases in a coordinated manner. Lactylation is a novel posttranslational modification (PTM) that links metabolism with epigenetics and affects disease progression. Therefore, analyzing the crosstalk between cellular metabolic and epigenetic factors in cardiovascular diseases is expected to provide insights for the development of new treatment strategies. The purpose of this review is to describe the relationship between metabolic and epigenetic factors in heart development and cardiovascular diseases such as heart failure, myocardial infarction, and atherosclerosis, with a focus on acylation and methylation, and to propose potential therapeutic measures.