One of the main reasons of death worldwide is cancer. There is a growing interest in the study of imidazolidinone derivatives where their synthesis and characteristics have been thoroughly discussed as appropriate precursors in pharmaceutical industry. Employing some drug design approaches such as divergence of substituents and hybridization of pharmacophores, a new set of imidazothiazines 5a-d have been designed and constructed. The structure of the prepared hybrids was asserted through spectral data. All synthesized conjugates were assayed for their seven dose anticancer assay against three carcinomas namely hepatic HepG2, mammary gland MCF-7, and prostate PC-3 carcinomas. The tested entities exerted promising anticancer activity toward the chosen carcinomas. Noticeably, compounds bearing 4-methoxy 5a or 4-hydroxy 5b groups with positive mesomeric action at phenyl ring on C-5 of imidazothiazine scaffold showed a more potent anticancer effect than compounds containing chloro group with a negative inductive effect 5c and 5d. Besides, the presence of carbonitrile functionality at C-6 of imidazothiazine ring as in 5c has a positive impact on the anticancer activity compared with the carboxamide moiety in 5d.