Purpose <p>This study aimed to investigate the role of pre-treatment neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) in the prognosis assessment of ¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) treated patients with advanced metastatic neuroendocrine tumors (NETs).</p> Methods <p>Eligible PRRT-treated patients (n = 247, 2010–2019) were included. Pre-PRRT NLR and MLR were calculated from complete blood count data. Data on tumor characteristics, response to PRRT, progression-free survival (PFS), and overall survival (OS) were evaluated using COXPH analyses.</p> Results <p>In NET patients, median values of NLR and MLR were 2.21 (IQR = 1.66–3.00) and 0.14 (IQR = 0.06–0.24), respectively. NLR showed significant positive association with G3 tumors (median = 3.64, IQR = 2.1–4.26, <i>p</i> = 0.022) and high ¹⁸F-FDG avidity (SUVmax&gt;5) (median = 2.5, IQR = 1.82–3.56, <i>p</i> = 0.003). MLR was significantly associated with high disease burden (median = 0.18, IQR = 0.08–0.29, <i>p</i> = 0.0083). MLR distinguished between the PRRT non-responders with progressive disease and responders with complete/partial response (median 0.19 versus 0.12, <i>p</i> = 0.043) or responders with stable disease (median 0.19 versus 0.14, <i>p</i> = 0.045). The ratios independently correlated with disease progression and OS. Patients in NLR^high (&gt;3.5) group displayed significantly shorter median PFS and OS (48 and 58 months) compared to NLR^low (≤3.5) group (108 and 96 months) (<i>p</i> &lt; 0.01). Patients in MLR^high (&gt;0.25) group displayed significantly shorter median PFS and OS (40 and 52 months) compared to MLR^low (≤0.25) group (108 and 102 months) (<i>p</i> &lt; 0.01).</p> Conclusion <p>Pre-treatment NLR and MLR had an independent prognostic impact on disease progression and OS in PRRT-treated NET patients. This routine, inexpensive CBC-based test in the standard pre-PRRT workup demonstrates the prognostic value and may aid clinicians in the risk stratification of NET patients.</p>