Osimertinib has been the standard treatment for advanced Epidermal Growth Factor Receptor (EGFR)-driven non-small cell lung cancer (NSCLC) for many years. However, even with remarkable response rate, progression-free survival (PFS) and survival benefit as compared to the old generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, treatment outcomes for these subsets of patients remain a challenge. Recently, in order to go beyond osimertinib, new treatment strategies have been developed. In particular, in the FLAURA 2 phase III randomized trial, the combination of platin-based chemotherapy and osimertinib showed impressive PFS benefits as compared to single-agent osimertinib. Furthermore, in the MARIPOSA phase III randomized study, the combination of the anti-EGFR and anti-MET monoclonal antibody amivantamab combined with the new anti-EGFR TKI lazertinib demonstrated remarkable PFS benefit as compared to single agent osimertinib. This paper will discuss these new treatment options and potential selection criteria for personalized treatment of patients.