Lung cancer is the second most common cancer with a poor survival rate (18.6%). Recently treatment of lung cancer has been improved starting from choosing appropriate treatment by gene and immunobiomarkers analysis to immunotherapy which played a major role in the treatment of lung cancer and showed improvement in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) with less adverse effects. Through this triad Immunotherapy, immunobiomarkers and Gene analysis oncologists can provide better treatment for lung cancer patients. The most important cause that makes immunotherapy shows good results in the treatment of lung cancer is P53 gene mutation which is present in more than half of lung cancer patients. P53 gene mutation causes high genetic instability so causes more mutations in cancer cells and more neoantigens are formed. These neoantigens make cancer cells more immunogenic and respond better to the treatment of lung cancer by immunotherapy. The most common immunotherapy drug family that is effective in the treatment of lung cancer is Immune checkpoint inhibitors. Throughout the journey of treatment Immune checkpoint inhibitors can develop resistance by multiple mechanisms that are discussed in the review and to overcome these mechanisms Immune checkpoint inhibitors can be used in combination with other immunotherapies or radiotherapy.