Background: Tuberous Sclerosis Complex (TSC) is a multisystemic neurocutaneous disorder in which hamartomas confer significant medical risks, including mortality, by disruption of local tissues. However, only recently have multiple studies assessed specific aetiologies of mortality in TSC. Methods: A literature review of all available studies examining mortality in TSC was conducted until December 15, 2024. Results: We identified 13 studies reporting 411 deaths from 6735 individuals with TSC. Crude mortality per 100 individuals ranged from 1.4-13.8 over average intervals of 11-45 years. Mortality risk ranged from 3.0-4.9 (mean 4.3) versus the general population. Mean life expectancy was 66.2 years compared to 81.8 in the general population. In seven studies that reported specific aetiologies of mortality, 6/7 (85%) had renal (commonly renal failure or angiomyolipoma hemorrhage) or brain disease (most frequently sudden unexpected death in epilepsy or brain tumours) as the most common cause of mortality. Intellectual delay conferred increased mortality risk. Lymphangioleiomyomatosis conferred significant risk of mortality in adult women and cardiac rhabdomyomas were the dominant cause of neonatal mortality. Conclusions: Mortality in TSC is elevated compared to the general population, with brain and renal disease most frequently culpable. Future studies should assess the impact of disease modifying therapies on mortality in TSC.