Zein, a corn-derived prolamine protein, has become a powerful ally in the fight against cancer, particularly non-small cell lung cancer (NSCLC.) Its unique attributes, enriched by modifiable hydroxyl and amino groups, have led to the development of advanced functionalised drug delivery systems. Innovative techniques like chemical crosslinking, desolvation, dispersion and micromixing have led to the creation of zein-based nanoparticles, revolutionising cancer therapy. Central to this examination is the remarkable ability of zein NPs to enhance drug stability, optimise oral bioavailability and improve targeted drug delivery, specifically tailored to combat NSCLC. This represents not just a technological breakthrough but a paradigm shift, ushering in a new era of precise, personalised and effective cancer treatment. Zein, a hydrophobic nanoparticle, is a promising drug for cancer treatment. However, its journey to the clinic is challenging due to its hydrophobic nature and the need for advanced evaluative platforms. This review emphasises the need for rigorous research to align zein's potential with real-world applications. It offers a synthesis of methodologies, applications, and obstacles, aiming to see zein nanoparticles as a central element in cancer therapy innovations. The review encourages researchers, clinicians and industry professionals to embrace the potential of zein and promote the convergence of laboratory innovation and clinical application.