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Caffeine’s metabolism is determined by CYP1A2 genotypes: AC/CC (SLOW) and AA (FAST). This trial evaluated CYP1A2 genotypes’ impact on exercise and cognitive effects in 36 resistance-trained females assessed under placebo (PL) and caffeine (6 mg/kg bw anhydrous caffeine-CAF) conditions, before ingestion and throughout the session. 23andMe^® (San Francisco, CA, USA) determined genotypes using saliva. Data were analyzed using two-way RMANOVA and paired-samples <i>t</i>-tests (<i>p</i> < 0.05). A significant main effect for genotype existed for leg press repetitions to failure (RTF) for CAF (<i>p</i> = 0.038), with the FAST group performing more repetitions than the SLOW (<i>p</i> = 0.027). There was a significant condition x genotype interaction for the subjective outcome index score (<i>p</i> = 0.045), with significant differences for time (<i>p</i> < 0.01) and between genotype (<i>p</i> < 0.001). Follow-up analysis revealed a higher total score (<i>p</i> = 0.028) following CAF for the FAST group and a lower total score (<i>p</i> < 0.01) in the SLOW group. Dizziness was reported following CAF in the SLOW group (<i>p</i> = 0.014; Cohen’s <i>d</i> = 0.725). Aside from leg press RTF, subjective outcome index score, and dizziness, the genotype groups experienced similar responses to resistance exercise performance and subjective mood states following caffeine ingestion.