Introduction Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by poor prognosis. Based on the KEYNOTE-522 trial, neoadjuvant pembrolizumab plus chemotherapy has become the standard of care due to significantly improved pathological complete response (pCR) rates. The presence of tumor-infiltrating lymphocytes (TILs) is a predictive biomarker of pCR. This retrospective cohort study examines a diverse patient population treated with the K522 regimen to determine if TILs predict pCR relative to other clinical and tumor-specific factors.Methods We retrospectively reviewed 187 patients with early-stage TNBC at two institutions (one tertiary care, one safety-net) who completed neoadjuvant K522 treatment between 2021–2024. Statistical analyses included Chi-squared tests, Z-tests, and univariate logistic regression to evaluate associations between TILs, ethnicity, tumor grade, and pCR.Results The overall pCR rate was 57%; TILs were present in 52.8% of cases. TILs were associated with a significantly higher pCR rate (70% vs. 48% without TILs; p = 0.0027). While pCR rates were similar across ethnicities, Hispanic patients with TILs had significantly higher pCR than those without (80.0% vs. 51.5%; p = 0.0254). Controlling for grade, patients with TILs were 2.442 times more likely to achieve pCR (CI: 1.310–4.553; p = 0.0050). Grade 3 tumors and node-positivity with TILs also showed statistically significant rates of pCR.Conclusion TILs serve as a strong predictive biomarker for immunotherapy response in a real-world TNBC population. Our findings regarding Hispanic and node-positive patients suggest TILs could guide treatment de-escalation to reduce K522-related toxicity. Standardizing TILs reporting is critical to optimizing treatment strategies and improving outcomes in underrepresented populations.