Objective: The paper examines the association of innovative antineoplastic drug use with cost structure, grouping performance, and payment deviations in tumor-related diagnosis-related groups (DRG), and compares hematologic malignancies with solid tumors. Methods: This single-center retrospective real-world study included 55425 inpatient cases from 54 tumor-related DRG groups at Hospital A from January 2024 to December 2025. The coefficient of variation (CV) and reduction in variance (RIV) were used to assess grouping performance. A 1∶1 propensity score matching (PSM) model based on age, length of stay, and surgical status was applied, followed by tumor-type subgroup analysis. Multivariable linear regression, single drug cost association analysis, DRG balance attribution, and a regression decision tree were performed to analyze cost and payment deviations. Results: Adding an innovative antineoplastic drug-use indicator reduced the weighted mean CV from 0.7719 to 0.7619 and increased the RIV from 0.5549 to 0.5647 in the original sample. After matching, 10732 cases were included. The RIV increased by 0.0513 overall, 0.0746 for hematologic malignancies, and 0.0518 for solid tumors. The drug-use indicator yielded an RIV greater than 0.5 in several DRG groups, including FM5B, FR1B, FW19, GJ1B, and FR21. After controlling for age, length of hospital stay, and surgery status, innovative antineoplastic drug use was associated with approximately 80.1% higher total hospitalization costs (P<0.001). Greater use of osimertinib, flumatinib, almonertinib, and several other agents was associated with lower DRG balances. The regression tree identified key dosage thresholds for recombinant human endostatin and other targeted agents. Conclusion: Innovative antineoplastic drug use provides additional explanatory value for within-group cost differences, but its grouping value varies across tumor types and DRG groups. Priority groups should be selected by jointly considering RIV, CV, sample size, cost gaps, and clinical interpretability, with refined grouping, transitional payment support, special-case review, and dynamic weight adjustment used in coordination.