The study introduces a novel platform called antibody-conjugated drug-loaded nanotherapeutics (ADN) to address the limitations of current treatments for non-small cell lung cancer (NSCLC). ADN combines immunotherapy and molecularly targeted therapy by attaching an anti-CD47 and anti-PDL1 antibody pair to a nanoparticle, which also contains the PI3K/AKT/mTOR pathway inhibitor PI103. The ADN was designed to target both innate and adaptive immune responses, as well as inhibit oncogenic pathways. In vitro and in vivo studies demonstrated that the ADN exhibited greater antitumor efficacy compared to current treatment options, particularly in aggressive lung cancer models. The ADN showed higher cellular internalization and cytotoxicity in cancer cells, with reduced toxicity in normal cells. The combination of anti-CD47 and anti-PDL1 antibodies on the nanoparticle enhanced the binding and internalization of the ADN, leading to improved therapeutic outcomes. The ADN platform offers a unified approach to improve outcomes in NSCLC treatment by targeting multiple immune checkpoints and delivering drugs specifically to tumor tissues.The study introduces a novel platform called antibody-conjugated drug-loaded nanotherapeutics (ADN) to address the limitations of current treatments for non-small cell lung cancer (NSCLC). ADN combines immunotherapy and molecularly targeted therapy by attaching an anti-CD47 and anti-PDL1 antibody pair to a nanoparticle, which also contains the PI3K/AKT/mTOR pathway inhibitor PI103. The ADN was designed to target both innate and adaptive immune responses, as well as inhibit oncogenic pathways. In vitro and in vivo studies demonstrated that the ADN exhibited greater antitumor efficacy compared to current treatment options, particularly in aggressive lung cancer models. The ADN showed higher cellular internalization and cytotoxicity in cancer cells, with reduced toxicity in normal cells. The combination of anti-CD47 and anti-PDL1 antibodies on the nanoparticle enhanced the binding and internalization of the ADN, leading to improved therapeutic outcomes. The ADN platform offers a unified approach to improve outcomes in NSCLC treatment by targeting multiple immune checkpoints and delivering drugs specifically to tumor tissues.