In this research, we delved into the predictive potential of three key markers – the neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and Onodera’s prognostic nutritional index (OPNI), in assessing lymph node metastases in breast cancer patients who had internal mammary lymph node involvement following thoracoscopic surgery. Our study revealed notable pathological distinctions between the groups with and without metastases, while age, tumor size, and histological grade exhibited no significant differences. The analysis unveiled statistically significant variances in NLR, SII, and OPNI when comparing these two groups. Multivariate analysis pinpointed NLR (OR = 1.503), SII (OR = 1.987), and OPNI (OR = 0.612) as robust predictors of lymph node metastases. Remarkably, combining these markers (AUC: 0.897) substantially enhanced the precision of predicting lymph node metastases compared to individual measurements (NLR: 0.749, SII: 0.717, and OPNI: 0.787). In conclusion, this study underscores the pivotal role of NLR, SII, and OPNI in predicting lymph node metastasis among breast cancer patients with internal mammary lymph node involvement post-thoracoscopic surgery, affirming our utility as reliable independent predictors of this critical clinical outcome.