Non‐small cell lung cancer (NSCLC) is the most common pathological type of lung cancer , accounting for approximately 85% of lung cancers. For more than 40 years, platinum (Pt)‐based drugs are still one of the most widely used anticancer drugs even in the era of precision medicine and immunotherapy. However, the clinical limitations of Pt‐based drugs, such as serious side effects and drug resistance, have not been well solved. This study constructs a new albumin‐encapsulated Pt(IV) nanodrug (HSA@Pt(IV)) based on the Pt(IV) drug and nanodelivery system. The characterization of nanodrug and biological experiments demonstrate its excellent drug delivery and antitumor effects. The multi‐omics analysis of the transcriptome and the ionome reveals that nanodrug can activate ferroptosis by affecting intracellular iron homeostasis in NSCLC. This study provides experimental evidence to suggest the potential of HSA@Pt(IV) as a nanodrug with clinical application. A novel albumin‐encapsulated Pt(IV) nanodrug (HSA@Pt(IV)), based on the Pt(IV) drug and nanodelivery system, exhibits superior delivery effect in both in vitro and in vivo models of non‐small cell lung cancer (NSCLC). HSA@Pt(IV) achieves antitumor effects by consuming glutathione and disrupting intracellular metal ion homeostasis, especially promoting Fe element accumulation to induce ferroptosis.