Simple SummaryLung cancer is the leading cause of cancer-related death worldwide according to the World Health Organization. Non-small cell lung cancer makes up the majority of cases. Immunotherapy with immune checkpoint inhibitors and targeted therapy with tyrosine kinase inhibitors and other molecular targeted agents significantly changed the treatment landscape and overall survival. Unfortunately, resistance to these treatments develops, and there is a need to identify additional innovative therapies that can overcome treatment resistance. Advancements in biomedical engineering and technology allowed for the development of novel agents, capable of delivering effective treatment directly to tumor cells. These agents include antibody drug conjugates and bispecific antibodies which have various targets and mechanisms of action, discussed in depth in this review.AbstractLung cancer is one of the most common cancers with the highest mortality. Non-small cell lung cancer (NSCLC) contributes to around 85% of lung cancer diagnoses (vs. 15% for small cell lung cancer). The treatment of NSCLC has vastly changed in the last two decades since the development of immunotherapy and targeted therapy against driver mutations. As is the nature of malignancy, cancer cells have acquired resistance to these treatments prompting an investigation into novel treatments and new targets. Bispecific antibodies, capable of targeting multiple substrates at once, and antibody–drug conjugates that can preferentially deliver chemotherapy to tumor cells are examples of this innovation. From our initial evaluation, both treatment modalities appear promising.