Lung cancer is the number one cancer killer globally. Thanks to the identification of several genetic drivers and the development of targeted therapeutics, the 5-year survival rate has improved in the last two decades, but the challenge remains to maintain therapeutic response and counteract resistance mechanisms over the long term. Genomics and proteomics can play a role in the therapeutic management of lung cancer. This chapter aims to provide an overview of lung cancer genomics and proteomics, polygenic risk, and the role these methods play in understanding lung tumor biology and directing treatment and care. Additionally, we will discuss the benefit of genomic testing, the identification of genetic and molecular signatures in lung cancer, and their current application to lung cancer treatment and care.