Objective <p>To investigate the predictive value of pretreatment ¹⁸F-NOTA-FAPI-04 PET/CT metabolic parameters combined with hematological biomarkers for pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC).</p> Methods <p>This retrospective study included 19 patients with locally advanced ESCC who underwent nCRT followed by surgery at Shandong Cancer Hospital from March 2022 to May 2023. Pretreatment clinical baseline data, ¹⁸F-NOTA-FAPI-04 PET/CT metabolic parameters, and hematological biomarkers were collected. Univariate and multivariate logistic regression analyses were used to select predictive parameters. A logistic regression model was constructed to predict pCR, and its performance was evaluated using receiver operating characteristic (ROC) curves, decision curves, and a nomogram.</p> Results <p>Among 19 patients, 11 achieved pCR, and 8 achieved non-pCR status. Univariate and multivariate analyses identified metabolic tumor volume (MTV) (OR = 0.978, <i>p</i> = 0.017) and platelet count (PLT) (OR = 1.003, <i>p</i> = 0.016) as independent predictors of pCR. By fitting a logistic regression model, the two-parameter joint model reached an AUC of 0.909, which was significantly better than the single indicator (MTV, AUC = 0.716; PLT, AUC = 0.761). The nomogram demonstrated that lower MTV (optimal threshold  ≤ 27.47) and higher PLT (optimal threshold  ≥ 330.5) values were associated with a higher likelihood of pCR.</p> Conclusion <p>Pretreatment ¹⁸F-NOTA-FAPI-04 PET/CT-derived MTV combined with PLT can noninvasively predict pCR after nCRT in ESCC patients, providing a basis for personalized treatment strategies.</p>