Phylomers are a class of peptides derived from fragments of biodiverse microbial genomes. The vast majority of cell-penetrating peptides (CPPs) identified to date are inefficient at intracellular delivery, as they often remain trapped within the endosomal compartment. This inefficiency has limited the feasibility of intracellular biologics. We have used Phylomer libraries to identify new CPPs for the delivery of macromolecules and nanoparticles into cells. Here we assess the ability of these novel cell-penetrating Phylomer peptides to deliver a functional cargo, Omomyc. The dominant-negative Omomyc is a c-Myc-derived basic, helix-loop-helix, leucine zipper (bHLHZip) mutant that is able to dimerize with c-Myc. Therefore, Omomyc competes with the formation of c-Myc/MAX complex and supresses transcription activation. The overexpression of Myc is involved in many types of human malignancies and in vivo overexpression of Omomyc strongly inhibits Myc-induced oncogenesis. However, Omomyc alone does not efficiently cross the cell membrane. Therefore, to achieve delivery of the Omomyc payload into breast cancer cells, we have produced a recombinant Phylomer-Omomyc fusion protein. We demonstrate that this Phylomer-Omomyc fusion effectively induces apoptosis in triple negative, drug resistant breast cancer cells and is more potent than Omomyc itself.