AbstractThe Hippo signaling pathway extorts several signals that concomitantly target the activity of transcriptional cofactor yes associated protein (YAP). YAP is a key regulator that elicits signature gene expression by coupling with transcriptional enhanced associate domain (TEAD) family of transcriptional factors. The YAP‐TEAD complex via target gene expression gets associated with the development, proliferation, and progression of cancerous cells. Moreover, YAP adorns cells with several oncogenic traits such as inhibition of apoptosis, enhanced proliferation, drug resistance, and immune response suppression, which later became associated with various diseases, particularly cancer. Therefore, inhibition of the YAP activity is an appealing and viable therapeutic target for cancer treatment. This review highlights the recent advances in existing and novel synthetic therapeutics targeting YAP inhibition and regulation. The synthetically produced YAPD93A belonging to cyclic peptides and DC‐TEADin02 and vinyl sulfonamide class of compounds are the most potent compounds to inhibit the YAP‐TEAD expression by targeting protein‐protein interaction (IC50 = 25 nM) and palmitate binding central pocket of TEAD (IC50 = 197 nM), respectively. On the other hand, Chlorpromazine belonging to phenothiazines class has the least potential to suppress YAP via proteasomal degradation (cell viability value of <20% at 40 µM).