Sepsis-induced myocardial injury ( SIMI) is a common and potentially fatal complication of sepsis. Its pathogenesis has not been fully elucidated, but involves multiple pathological processes, including excessive inflammatory response, mitochondrial dysfunction, apoptosis, and oxidative stress. Current clinical interventions primarily include fluid resuscitation, vasoactive agents, and anti-inflammatory therapies; however, their efficacy remains limited, and they fail to reverse pathological remodeling at the epigenetic level. This systematic review summarizes the result of studies on epigenetic modifications, including DNA methylation, histone modifications (acetylation, methylation), and non-coding RNA regulation, in relation to septic myocardial injury. The review aims to provide novel perspectives to aid in the early warning, diagnosis, treatment, and targeted drug development of SIMI, thereby improving the prognosis of patients with this condition.