Early diagnosis through noninvasive tools is a cornerstone in the realm of personalized and medical healthcare, averting direct/indirect infection transmission and directly influencing treatment outcomes and patient survival rates. In this context, optical biochip breathomic sensors integrated with nanomaterials, microfluidics, and artificial intelligence exhibit the potential to design next-generation intelligent diagnostics. This cutting-edge tool offers a variety of advantages, including being economical, compact, smart, point of care, highly sensitive, and noninvasive. This makes it an ideal avenue for screening, diagnosing, and prognosing various high-risk diseases/disorders by detecting the associated breath biomarkers. The underlying detection mechanism relies on the interaction of breath biomarkers with sensors, which causes modulations in fundamental optical attributes, such as surface plasmon resonance, fluorescence, reflectance, absorption, emission, phosphorescence, and refractive index. Despite these remarkable attributes, the commercial development of optical biochip breathomic sensors faces challenges, such as insufficient support from clinical trials, concerns about cross-sensitivity, challenges related to production scalability, validation issues, regulatory compliance, and contrasts with conventional diagnostics. This perspective article sheds light on the cutting-edge state of optical breathomic biochip sensors for disease diagnosis, addresses associated challenges, proposes alternative solutions, and explores future avenues to revolutionize personalized and medical healthcare diagnostics.