<b><i>Purpose:</i></b> There is increasing evidence that a persistent systemic inflammatory response predicts lower survival in patients with malignant disease. The modified Glasgow Prognostic Score (mGPS) is defined by a combination of elevated C-reactive protein (CRP) (&#x3e;10 mg/L) and hypoalbuminemia (&#x3c;35 g/L). It is considered as an independent prognostic marker in several organ malignancies. The aim of this study was to investigate the value of mGPS in metastatic penile carcinoma in predicting treatment response and survival. <b><i>Methods:</i></b> One hundred and fifty-six patients with penile carcinoma treated with chemotherapy were included in this retrospective study. The mGPS before chemotherapy was classified into 3 groups (mGPS 0 [CRP &#x3c;10, any albumin], mGPS 1 [CRP &#x3e;10 mg/L, albumin &#x3e;35 g/L], and mGPS 2 [CRP &#x3e;10 mg/L, albumin &#x3c;35 g/L]). Overall survival and disease-free survival were calculated by Kaplan-Meier analysis and chemotherapy toxicity by CTC criteria. Univariate Cox proportional hazards models were calculated to estimate the effect of each predictor on OS and DFS. <b><i>Results:</i></b> Survival was significantly different in the 3 mGPS classes, with mGPS 0 patients showing the best treatment response and survival. Univariate analysis showed that mGPS (<i>p</i> &#x3c; 0.0001), tumor stage (<i>p</i> = 0.004), and venous and lymphatic invasion (<i>p</i> = 0.011) were factors independently associated with prognosis. The response to chemotherapy differed significantly between mGPS groups (mGPS 0, 36/51 [71%]; mGPS 1, 24/70 [34%]; mGPS 2, 9/35 [26%], <i>p</i> = 0.03 and <i>p</i> = 0.37, respectively). mGPS was significantly associated with chemotherapy-associated toxicity, with treatment adaptation (<i>p</i> &#x3c; 0.01) and toxicity-related deaths (<i>p</i> = 0.028). <b><i>Conclusions:</i></b> Systemic inflammatory response and nutritional status as expressed by the mGPS are independent predictors of treatment response, chemotherapy-associated toxicity, and survival in metastatic penile carcinoma. In addition to other known pathological markers of tumor aggressiveness, the mGPS can be used as a clinical predictor of prognosis.