Lung cancer is the second most prevalent cancer and the leading cause of cancer‐related death worldwide. Surgery, chemotherapy, molecular targeted therapy, immunotherapy and radiotherapy are currently available as treatment methods. However, drug resistance is a significant factor in the failure of lung cancer treatments. Novel therapeutics have been exploited to address complicated resistance mechanisms of lung cancer and the advancement of nanomedicine is extremely promising in terms of overcoming drug resistance. Nanomedicine equipped with multi‐functional and tunable physiochemical properties in alignment with tumor genetic profiles could achieve precise, safe, and effective treatment while minimizing or eradicating drug resistance in cancer. Here, we review the discovered resistance mechanisms for lung cancer chemotherapy, molecular targeted therapy, immunotherapy and radiotherapy, and outline novel strategies for the development of nanomedicine against drug resistance. We focus on engineering design, customized delivery, current challenges and clinical translation of nanomedicine in the application of resistant lung cancer.This article is protected by copyright. All rights reserved