Over the past few decades, the concept of precision medicine has drastically transformed the field of medical oncology; the implementation of patient-tailored therapies has improved significantly. Liquid Biopsy It is a revolutionary technique that opens up previously unexpected possibilities. It consists of the detection and isolation of circulating tumor cells, circulating tumor DNA, and exosomes, as a source of genomic information in cancer patients. The identification of predictive biomarkers Tumor tissue analysis is now essential for optimal patient care, but it faces several biological and technological challenges. A recent study of multiple samples from lung cancer patients demonstrated that there is intratumoral heterogeneity between different regions within the same tumor (spatial heterogeneity), as well as between the primary tumor and local or distant recurrences in the same patient (temporal heterogeneity). In addition, other studies have characterized the dynamic changes in tumor characteristics over the course of the disease, and these changes have affected the treatment resistance. Therefore, inter- and intratumoral heterogeneity poses a fundamental challenge for guiding clinical decision-making in pulmonary oncology, since the Tissue biopsies can be inaccurate to capture the complete genomic profile of a cancer patient.