Diagnosis and intervention at the earliest stages of cancer are imperative for maximizing patient recovery outcomes and substantially increasing survival rates and quality of life. Recently, to facilitate cancer diagnosis, volatile organic compounds (VOCs) have shown potential with unique characteristics as cancer biomarkers. Various insects with sophisticated sensitivities of odor can be quickly and readily trained to recognize such VOCs using olfactory-linked skills. Furthermore, the approach to analyzing VOCs can be made using electronic noses, commonly referred to as e-noses. Using analytical instruments like GC-MS, LC-MS/MS, etc., chemical blends are separated into their constituent parts. The significance of odorant receptors in triggering neural responses to ambient compounds has received great attention in the last twenty years, particularly in the investigation of insect olfaction. Sensilla, a sophisticated olfactory neural framework, is regulated by a neuronal receptor composed of neuronal, non-neuronal, extracellular lymphatic fluid with an effectively generated shell. This review provides an in-depth exploration of the structural, functional, and signaling mechanisms underlying odorant sensitivities and chemical odor detection in the excretory products of cancer patients, addressing current challenges in VOC-based cancer diagnostics and innovative strategies for advancement while also envisioning the transformative role of artificial olfactory systems in the future of cancer detection. Furthermore, the article emphasizes recent preclinical and clinical advancements in VOC applications, highlighting their potential to redefine early diagnostic approaches in oncology.