Gene delivery gained great attention as an advanced molecular biology technique for preventing and treating genetic disorders by allowing fundamental modification of gene expression, editing, and knocking down of genes in the host genome. Nonviral vector formulations comprising cationic lipids, polymers, dendrimers, and peptides offer a potential modes for compacting oligonucleotides for in vitro and in vivo delivery. In our study, we are developing A multicomponent peptide-based system incorporating a receptor-targeting ligand peptide that can target overexpressed receptors as a molecular target for tumor targeting; cationic peptides that can condense negatively charged oligonucleotide and make nanostructured complexes; and endosomal disrupting peptide for assisting endosomal release. A highly efficient microwave-assisted 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesizer was used to synthesize the complex multi-component peptide-based systems where different peptides can be coupled into a single entity. The peptide system was successfully synthesized, purified, and evaluated for its potency as a gene delivery vector. The optimized peptide-based delivery systems were further co-formulated with different phospholipids to investigate their biocompatibility and serum stability. Parameters that were applied to investigate the efficacy of the co-formulation approach of the systems include examining complex size and charge, receptor targeting, level of expression, toxicity, stability, and compatibility in the presence of serum. Here, the formulation approach of non-viral multicomponent receptor-targeted nanocomplexes demonstrated that peptide systems facilitated receptor-mediated cell uptake; packaging of oligonucleotides into nanoparticles; and the phospholipid component exhibited endosomal release and comparable and stable transfection efficiency at serum and serum-free environment. The results suggested a progression of further developing an efficient and safe targeted nonviral oligonucleotide carrier for future in vivo studies.