Soccer performance, particularly regarding the physical demands of matches, can be influenced by genetic factors. This chapter initially discusses some of the main genetic polymorphisms that have been associated in the literature with physical performance in soccer, with special attention to genes more directly related to the ability to sustain high training intensities as well as those associated with the risk of musculoskeletal injuries involving muscles, tendons, and ligaments, which influence skeletal muscle structure, vascular tone regulation, and metabolic responses to exercise. The chapter therefore provides a detailed exploration of polymorphisms in the following genes: ACTN3, ACE, MCT1, COL5A1, COL1A1, and MMP3. In addition, it addresses polymorphisms in other genes related to vasodilatory responses (NOS3, BDKRB2, ADRB2) and metabolic responses (the PPAR family and CPK), as well as polymorphisms in genes involved in the modulation of immunoinflammatory and oxidative stress responses, such as IL-6, TNF-α, CRP, SOD, CAT, and GPX. Finally, the chapter presents reports from our studies and intervention experiences with male and female soccer players, both from youth development squads and professional teams. Throughout the chapter, practical applications of the theoretical content are proposed, grounded in our empirical experiences and scientific studies with soccer athletes.