In particular, two different technical approaches can be applied on cfDNA: the first one is a targeted approach focused on high deep analysis of a few driving lesions—TP53 gene and other genes, e.g., BRCA1 and BRCA2, which is helpful to guide PARPi therapy decisions—while the second one is represented by an untargeted approach such as sWGS, which is able to capture the great genomic aberrations, estimate the cfDNA TF and to capture the biological tumor evolution. This evidence concerns the gene TP53 and neoplasm.