Sepsis-induced myocardial injury (SIMI) is a common and critically fatal complication of sepsis. Its pathogenesis has not been fully elucidated, involving multiple pathological processes such as excessive inflammatory response, mitochondrial dysfunction, apoptosis, and oxidative stress. Although current clinical interventions primarily include fluid resuscitation, vasoactive agents, and anti-inflammatory therapies, their efficacy remains limited and fails to reverse pathological remodeling at the epigenetic level. This article systematically summarizes and discusses studies on epigenetic modifications—including DNA methylation, histone modifications (e.g., acetylation, methylation), and non-coding RNA (ncRNA) regulation—in relation to septic myocardial injury. The review aims to provide novel perspectives for early warning, diagnosis, treatment, and targeted drug development for SIMI, thereby improving the prognosis of patients with sepsis-induced myocardial injury.