Rhabdomyolysis is a clinical emergency characterized by acute skeletal muscle breakdown, which in severe cases results in a life-threatening condition, often leading to renal failure. The pathophysiology of RM is highly complex and multifactorial, involving genetic and environmental factors as key contributors. Despite progress in understanding the genetic factors contributing to rhabdomyolysis, their relative significance and interactions with environmental factors remain largely unknown. To address these challenges and identify the association of different extrinsic triggers and their associated genetic risk factors, we performed a retrospective longitudinal study in a cohort of 2304 rhabdomyolysis patients and 18,134 controls. This led to an enrichment of a number of new and previously known environmental factors in RM patients compared to controls. To conduct genetic analysis, we compared the genetic mutations identified in these patients with a group of 46,714 controls exhibiting a comparable comorbidities distribution. This resulted in identifying known and novel variants. As preventive genomics is increasingly integrated into clinical care, a comprehensive analysis of the external triggers and their association with genetic susceptibility will help assess and finally reduce the risk of life-threatening complications and significantly improve the quality of life for RM patients.