Background: Colorectal cancer (CRC) remains a significant global health concern, ranking as the third most common cancer worldwide and the second leading cause of cancer-related mortality. The folate receptor-alpha (FR-α), a glycosylphosphatidylinositol (GPI)-anchored membrane protein, this overexpression presents a compelling opportunity for targeted drug delivery. Aim: This research aimed to develop an FR-α targeted nanocarrier system for the precise delivery of an anticancer agent, thereby minimizing off-target effects and systemic cytotoxicity to normal cells. Methodology: The targeted nanocarrier formulations were prepared by conjugating folic acid (FA)/Premetrexed and anticancer agents . Polymeric micelles were developed using an ethanol injection method to achieve a sustained-release formulation. Various excipients and block polymeric materials, including Pluronic P123, D1 lipids, and Transcutorl HP, were utilized. The final formulations were rigorously characterized for particle size, surface charge (zeta potential), morphology, drug loading efficiency, and in vitro drug release kinetics. Furthermore, the cellular inhibitory effects and cytotoxicity were evaluated in vitro against colon cancer cell lines (CT-26 and HT29) and a normal human embryonic kidney cell line (HEK 293). Results: The formulations demonstrated nano size particle range (500 ± 25 nm) and a sustained drug release, with ~ 67 ± 5% of the drug released over 72 hours in PBS (pH 7.4). High drug loading efficiency of 73 ± 2% was achieved, indicating a significant payload capacity. In cellular studies, the targeted formulations achieved 50% cell inhibition (IC50) at a concentration of 0.250 µM, significantly lower than the 0.585 µM observed for non-targeted formulations. Critically, the targeted formulations exhibited markedly reduced cytotoxicity in the normal HEK 293 cell line. Conclusion: Our findings reveal that the FR-α targeted drug delivery system effectively ameliorates colon cancer, even at advanced stages.​ We also find the challenges in conjugation rection, however more hypothetical experiments would be required to establish the chemical conjugation. Upon this issue we had used pemetrexed as potent antifolate ligand instead of folic acid.