The study of the effects of genetic polymorphisms in inflammatory response markers and antioxidant enzymes on physical performance has attracted increasing interest. The aim of this chapter is to elucidate the mechanisms through which these effects occur and to promote the understanding of how such polymorphisms impact performance across different sport modalities with distinct physiological demands. Various polymorphisms in pro-inflammatory cytokines, such as IL-6, TNF-α, and C-reactive protein, as well as in antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, are presented. The main effects of these polymorphisms on the performance of athletes and physically active individuals are discussed, including references to certain clinical conditions potentially associated with these polymorphisms, due to chronic inflammation or oxidative stress. For each cytokine and antioxidant enzyme, a brief review of their physiological roles is provided to facilitate the understanding of the underlying mechanisms by which these polymorphisms may influence sports performance. Throughout the discussion of each component, reflections and critical considerations are encouraged regarding the practical applications of this knowledge to optimize individual genetic potential through targeted training strategies.