Background: This present study aimed to assess if clinical, laboratory and MRI were an accurate benchmark in assessing the effectiveness of neoadjuvant chemotherapy in osteosarcoma patients. Methods: This was an observational analytic study with a cross-sectional design. We correlated among clinical, laboratory and magnetic resonance imaging (MRI) data before and after neoadjuvant chemotherapy; and percentage of tumor necroses from osteosarcoma patients during the period between January 2017–July 2019. Results: Of the 58 patients included in this study, 38 were male and 20 were female aged 5 - 67 years (mean: 16-year-old. 37(63.8%) patients underwent neoadjuvant chemotherapy with CAI regimens and 13 (36.2%) with CA regiments. The tumors were classified as stage IIB in 43 (74.1%) patients and stage III in 15 (25.9%) patients. Wilcoxon test showed significant differences between alkaline phosphatase (ALP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR) before and after neoadjuvant chemotherapy in the poor-response group. We found no significant difference between lactic dehydrogenase (LDH) and lymphocyte-to-monocyte ratio (LMR) before and after neoadjuvant chemotherapy in the good-response group. MRI revealed decreased tumor volume in patients in the good-response to chemotherapy. Conclusion: We demonstrated that ALP level was statistically significant in the poor-response group. We also found that LDH value before neoadjuvant chemotherapy had a strong correlation with degree of necrosis and could be used as a predictive indicator. MRI plays an important role in evaluating tumor volumes and preoperative radiological changes to predict histological necrosis. © 2021