Cancer remains a formidable global health challenge, underscoring the critical need for early and accurate diagnostic tools. In recent years, nanotechnology has emerged as a promising frontier in cancer detection, offering innovative approaches to enhance sensitivity, specificity, and convenience in diagnostics. This comprehensive review delves into the intersection of nanotechnology and sputum-based assays for cancer detection. Sputum, a readily accessible biomarker source, has gained increasing attention due to its potential to house early cancer biomarkers. By harnessing the unique properties of nanoparticles, this review explores how nanotechnology is revolutionizing sputum- based cancer detection. We examine the intrinsic attributes of sputum as a diagnostic fluid, the diverse applications of nanoparticles, and the evolving landscape of cancer-specific biomarkers. Moreover, we provide insights into various nanotechnology assay techniques and their clinical implications while highlighting the challenges and future prospects in this dynamic field. This review aims to elucidate the transformative impact of nanotechnology on cancer diagnostics through sputum, offering a roadmap towards earlier and more accurate cancer detection.