This narrative review explores the relationship between genetics and elite endurance athletes, summarizes the current literature, highlights some novel findings, and provides a physiological basis for understanding the mechanistic effects of genetics in sport. Key genetic markers include ACTN3 R577X (muscle fiber composition), ACE I/D (cardiovascular efficiency), and polymorphisms in PPARA, VEGFA, and ADRB2, influencing energy metabolism, angiogenesis, and cardiovascular function. This review underscores the benefits of a multi-omics approach to better understand the complex interactions between genetic polymorphisms and physiological traits. It also addresses long-standing issues such as small sample sizes in studies and the heterogeneity in heritability estimates influenced by factors like sex. Understanding the mechanistic relationship between genetics and endurance performance can lead to personalized training strategies, injury prevention, and improved health outcomes. Future studies should focus on standardized classification of sports, replication studies involving diverse populations, and establishing solid physiological associations between polymorphisms and endurance traits to advance the field of sports genetics.