There is evidence that both intra-serial variable resistance (I-sVR), as pre-activation within the post-activation performance enhancement cycle (PAPE), and creatine and caffeine supplementation increase athletic performance in isolation. However, the effect of the three conditioning factors on 30 m repeated sprint ability (RSA) performance in young soccer players is unknown. This study determined the summative and isolation effect of ergogenic aids and pre-activation in half-back squats (HBSs) with I-sVR on performance in an RSA test in young soccer players. Twenty-eight young soccer players were randomly assigned to either EG ( = 7, creatine + caffeine + I-sVR), EG ( = 7, creatine + placebo + I-sVR), EG ( = 7, placebo + caffeine + I-sVR), or EG ( = 7, placebo + placebo + I-sVR), using a factorial, four-group-matched, double-blind, placebo-controlled design. Creatine supplementation included 0.3 g/kg/day for 14 days, caffeine supplementation included 0.3 mg/kg per day, and pre-activation in HBS with I-sVR (1 × 5 at 30% 1RM [1.0-1.1 m/s] + 1 × 4 at 60% 1RM [0.6-0.7 m/s]). The RSA test and HBS outcomes were evaluated. Three-way ANOVA showed non-significant differences for the RSA test and HBS outcomes ( > 0.05). At the end of this study, it was found that the three ergogenic aids, together, do not generate a summative effect on the physical performance of young soccer players. However, it is important to analyze individual responses to these specific protocols.