Background <p>This study aimed to evaluate the distinct prognostic value of [¹⁸F]FDG and [⁶⁸Ga]Ga-PSMA-11 PET imaging in advanced hormone-sensitive prostate cancer, highlighting their complementary roles at both patient and lesion levels.</p> Methods <p>This study retrospectively included 298 patients with newly diagnosed prostate cancer who underwent baseline dual-tracer PET imaging. Quantitative PET parameters for both [¹⁸F]FDG and [⁶⁸Ga]Ga-PSMA-11 were extracted. Clinical outcomes, including progression-free survival, biochemical response, and radiographic response, were collected during follow-up. Lesion-based analysis was performed in 267 measurable lesions to evaluate the association between tracer uptake and local radiographic response, as determined by changes in lesion diameter following systemic therapy.</p> Results <p>Here we show that higher whole-body [¹⁸F]FDG uptake, including total lesion glycolysis (HR = 3.525, <i>p</i> &lt; 0.001) and metabolic tumor volume (HR = 2.757, <i>p</i> &lt; 0.001), is significantly associated with shorter progression-free survival. In contrast, only PSMA-derived tumor volume (HR = 2.019, <i>p</i> = 0.018), but not total lesion PSMA uptake (HR = 1.438, <i>p</i> = 0.221), demonstrates prognostic value. Moreover, patients with higher whole-body [¹⁸F]FDG burden receive greater benefit from chemotherapy (HR = 2.936, <i>p</i> = 0.004). At the lesion level, higher [⁶⁸Ga]Ga-PSMA-11 uptake is significantly correlated with more favorable radiographic response (<i>p </i>&lt; 0.001), while lesion-level [¹⁸F]FDG uptake does not demonstrate predictive value.</p> Conclusions <p>[¹⁸F]FDG PET and [⁶⁸Ga]Ga-PSMA-11 PET provide distinct but complementary prognostic value in advanced hormone-sensitive prostate cancer. Dual-tracer PET imaging enhances prognostic accuracy and provides comprehensive guidance for individualized treatment strategies.</p>