Background: Neoadjuvant chemotherapy (NACT) has been strongly recommended for patients diagnosed with TNBC or HER2+ breast cancer. Hispanic populations are composed of a heterogenous group that include different racial and national backgrounds. This may account for differences in response to NACT. The aim of this study is to explore the factors associated with chemosensitivity among Hispanic women with early-stage TNBC or HER2+ breast cancer in the United States. Methods: This retrospective cohort study queried data from the National Cancer Database between 2010 and 2020 for women diagnosed with early-stage TNBC or HER2+ breast cancer who received NACT and identify as Hispanic (Mexican, Puerto Rican, Cuban, South or Central American and Dominican Republic). Patients were divided into two groups based on their response to NACT: sensitive (pTNM stage < cTNM, including ypT0N0) and refractory (pTNM stage ≥ cTNM stage). Using chi-square, socio-demographic and clinical factors associated with response to NACT were identified. Significant variables (p<0.05) were included in the multivariate logistic regression model predicting their response to NACT. Results: This study included N= 1,225 Hispanic women who met the inclusion criteria, 48.8% were Mexican, and 30.5% were from the Caribbean (Cuba, Puerto Rico, and Dominican Republic and 20.7% were from Central or South America). Within the overall group, n=769 (62.8%) were deemed sensitive to NACT, while n=456 (37.2%) were considered refractory. Significant variables associated with chemosensitivity at the multivariate level included age, tumor subtype, cN stage, and the use of multiagent NACT. Hispanic patients >70 years were less likely to respond to NACT (OR 0.57 95% CI 0.35-0.94, p-value=0.027). Meanwhile, patients diagnosed with TNBC were more likely to respond to NACT compared to HER2+ tumors (OR 2.0 95%CI 1.6-2.6, p-value<0.001). Patients with negative lymph nodes were 1.6 times more likely to have chemosensitive response compared to those with positive lymph nodes who tend to have more refractory disease (95%CI 1.6-2.6, p-value<0.001). Patients receiving single agent were 63% less likely to respond than multiagent NACT (95%CI 0.23-0.61, p-value<0.001). No major chemosensitive differences were found between individual Hispanic origin. Conclusions: In our nationwide Hispanic cohort, youngerage, TNBC, and cN0 were found to be significant predictors of neoadjuvant chemosensitive response in early-stage Breast Cancer. Further prospective inclusive studies are warranted to better delineate the heterogeneity in response to NACT among individual self-reported Hispanic ethnicities within the United States.