The new series of sulfa azo 4H-chromene esters (7a–g, 8, and 11a–e) were adapted and assessed for their inhibitory behavior against the HCT-116, MCF-7, and HepG-2 tumor cell lines, targeting EGFR, MMP-2, and Carbonic anhydrase CAII. The gene discussed is MMP2; the disease is neoplasm.