For non-small cell lung cancer (NSCLC) patients receiving neoadjuvant therapy, the major pathologic response (MPR) is defined as the percentage of residual viable tumor cells (%RVT) in the tumor bed of no more than 10%. It has been proposed as a predictor of survival in neoadjuvant therapy-treated cohorts. Nonetheless, the significance of %RVT in the pathological assessment of lung adenocarcinoma cohorts remains undetermined. Overall, 152 lung adenocarcinoma patients were included in this retrospective study, among whom 67 received neoadjuvant targeted therapy and 85 received neoadjuvant chemotherapy. Clinicopathological characteristics, neoadjuvant treatment response, and survival status were investigated. The routinely adopted standard for MPR (%RVT ≤10%) failed to differentiate prognosis in the lung adenocarcinoma population. For the neoadjuvant chemotherapy cohort, the optimal %RVT cutoff value of RFS was 60%. However, this cutoff value was clinically insignificant in the neoadjuvant targeted therapy cohort. Hence, for these patients, we built a nomogram model including high-grade patterns and ypN stage to predict disease recurrence, demonstrating a high efficacy (a bootstrap-corrected C-index of 0.731). %RVT served as a strong indicator of the prognosis of lung adenocarcinoma in patients receiving neoadjuvant chemotherapy but not neoadjuvant targeted therapy. Residual high-grade pathological patterns might substitute MPR in prognostic evaluation of lung adenocarcinoma post-targeted therapy.