Background: The clinical outcome of Non-Small Cell Cancer (NSCLC) has been advanced with molecular targeted therapy. To our knowledge, there is no data addressing targeted therapy outcomes based on race. Here, we focus on racial differences in response to targeted therapy in NSCLC. Methods: From a total of 1396 NSCLC patient between 2013 and 2017, 330 of them underwent targeted-exome sequencing. We conducted a matched study by propensity score generated using logistic regression with, sex, race, age, smoking, surgical resection, Immunotherapy and tumor stage as covariates. We used 258 genomic sequenced matched to 774 non-sequenced patients (1:3 match) to evaluate the outcomes (OS, PFS) of seven targeted gene therapies (EGFR, ALK/EML, MET, BRAF, ROS1, ERBB2, RET) using Kaplan-Meier method. Results: Of the 258 matched patients with genomic sequencing, 123 had at least one of the seven targeted gene mutations and 80 patients received targeted therapy (66% Caucasians, 24% African American (AA) , 10% others). The percentage of patients receiving targeted therapy for their tumors was 94% with EGFR (60/77), 35% with MET (6/17), 100% with ALK/EML (6/6), 0.05% with BRAF (1/19), 20% with RET (1/5), 50% with ROS1 (1/2), and 62% with ERBB2 (5/8) mutations. Independently from treatment types,those ones with genomic sequencing had significantly better OS (P = 0.002, 25.3 Vs. 14.6 months) and PFS (P = 0.008, 21.8 Vs. 12.3 Months) compared to non-sequenced matched control subjects. Patients who underwent targeted genomic therapy had both better OS (35.2 Vs. 28.3 m, P = 0.03) and PFS (29 Vs. 16.3 m, P = 0.01). There was no significant racial difference in baseline characteristics and driver mutation frequency (p = 0.47) except that ALK/EML had a higher mutation rate in AA (P = 0.019). No racial disparity in receiving targeted therapy (P = 0.45) was observed. Notably, Caucasian patients with mutant EGFR or ALK had significantly better OS (P = 0.01, 34.2 Vs. 14.9 m) and PFS (P = 0.02, 24.4 Vs.13.5) compared with AA patients. Conclusions: Genomic sequencing and targeted therapy increased survival outcomes in advanced NSCLC patients. Caucasians harboring EGFR or ALK/EML mutations had better survival compared to AAs.