Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, with high postoperative recurrence and metastasis rates posing significant challenges to patient survival. Identifying reliable and accessible prognostic markers is essential for optimizing treatment strategies. This study investigates the prognostic significance of two preoperative hematological indices, the [neutrophils × platelets]/[lymphocytes × hemoglobin] (NP/LHb) ratio and absolute monocyte count (Mono), in predicting overall survival in CRC patients. A retrospective analysis of 566 patients was conducted, with one cohort serving as an external validation set. Receiver operating characteristic curve analysis identified optimal cut-off values for NP/LHb and Mono, and Kaplan-Meier survival analysis revealed that higher levels of both markers were associated with significantly shorter survival. A novel prognostic model, NPM, integrating NP/LHb and Mono, demonstrated superior predictive accuracy compared to either marker alone. The NPM model was further validated through a nomogram, achieving high predictive performance for 1-, 3-, and 5-year survival. These findings highlight the potential of combining inflammatory and nutritional markers for effective risk stratification in CRC patients. The NPM model offers a simple, cost-effective prognostic tool that may facilitate personalized postoperative management, though further prospective validation is warranted.