Various systemic immunomodulating therapies (SITs) have been used to treat toxic epidermal necrolysis (TEN) but their efficacy remains unclear.To perform a systematic review and network meta-analysis (NMA) evaluating the effects of SITs on mortality for Stevens-Johnson syndrome (SJS)/TEN overlap and TEN.A literature search was performed in online databases (from inception to Oct 31, 2019). Outcomes were mortality rates and SCORe of Toxic Epidermal Necrolysis (SCORTEN)-based standardized mortality ratio (SMR). A frequentist random-effects model was adopted.Sixty-seven studies involving 2079 patients were included. An NMA of 10 treatments revealed that none was superior to supportive care in reducing mortality rates and that thalidomide was associated with a significantly higher mortality rate (Odds ration [OR], 11.67; 95% confidence interval [CI], 1.42-95.96). For SMR, an NMA of 11 treatment arms demonstrated that corticosteroids and intravenous immunoglobulin (IVIg) combination therapy was the only treatment with significant survival benefits (SMR, 0.53; 95% CI, 0.31-0.93).Heterogeneity and a paucity of eligible randomized controlled trials.Combination therapy with corticosteroids and IVIg may reduce mortality risks in patients with SJS/TEN overlap and TEN. Cyclosporine and etanercept are promising therapies but more studies are required to provide clearer evidence.