The FASN is essential enzyme in de novo fatty acid synthesis that converted into phospholipids which provides resistance to drug uptake in malignancies. The FASN over expression and intrinsic/acquired both types of drug resistance reported in carcinomas. To assess the FASN up-regulation overall therapeutic response in drug screened cancer cell line data from Cancer Cell Line Encyclopedia (CCLE) by a rational CCLE GDSC gene expression - drug sensitivity correlations tool. We identify differential response of FASN in different drug treated tissue in which few cancer studies the drug performance increases in presence of FASN over expression but several cancer studies showed drug resistance by FASN over expression. The FASN increased expression drug resistance mainly linked with MAPK, EGFR, AKT, BCR/ABL, MDM2, HDAC and IGFR pathways that are responsible for angiogenesis, growth, survival, migration, differentiation and proliferation. Our study signifies the FASN elevated expression resistance to anti-proliferatory drugs for multiple oncogenes which indicate the FASN inter/intra-pathway interactions with oncogenes for their effective survival. We diagnose the FASN over expression as predictive marker in drug resistance genomes to design molecular medicines that consider it secondary target in generally accepted therapy.