The assessment of body composition over a competitive season provides valuable information that can help sports professionals to evaluate the efficacy of training and nutritional strategies, as well as monitoring athletes’ health status. The purpose of this study was to examine the association of changes in body composition and hydration status with changes in lower-body neuromuscular performance in soccer. Twenty-two male professional soccer players (mean ± SD; age: 26.4 ± 4.8 years; height: 184.3 ± 5.7 cm; body mass: 81.1 ± 6.5 kg; body fat: 11.6 ± 1.5%) took part in the study, for which they were tested at the initial and final stage of the competitive season. Total (whole body) and regional (arms and legs) lean soft tissue (LST) were estimated to obtain the body composition profile. Total body water (TBW) content, including extracellular (ECW) and intracellular (ICW) water, was obtained to monitor players’ hydration status. Countermovement jump (CMJ) height, power, and strength were used to derive players’ lower-body neuromuscular performance. The results showed that changes in legs LST and ICW significantly (p < 0.01) explained (r2 = 0.39) the improvements in CMJ height, power, and strength from the initial to the final stage of the season. Given the high demand imposed on the lower limbs during a soccer season, being more susceptible to change compared to whole-body LST, assessing regional LST and ICW would be more appropriate to provide extended information on players’ readiness.