The invention/demonstration of RNA interference (RNAi) as a therapeutic agent has opened the doors to development/research. Clinical trials on siRNA usage demonstrate that it may be utilized as a safe, effective and well-tolerated drug to treat a range of illnesses, particularly cancer. The siRNA drug delivery technology is useful in that it is easy to build and alter to reach the target site. Despite great advances in creating effective in vivo siRNA administration, there are still several difficulties and hurdles to face in order to reach the optimum formulation in terms of selectivity, efficiency and security of delivery. Chemical modifications, liposome-mediated transport, polymeric nanoparticles, and conjugated nanoparticles can bypass this. These changes have minimized off-target effects at various places and positions, resulting in better siRNA duplex nuclease and heat stability. Nanoparticles linked to the targeted ligand improve the probability of tumor-specific receptor binding. Controlling siRNA specificity, intercellular trafficking and site-specific delivery are all issues in the siRNA delivery method. The next study should focus on the in vivo safety profiles of different delivery systems, as well as creating possible targeting techniques for siRNA distribution that would limit toxicity, off-target effects, and other concerns. It is also vital to optimize biodegradable and biocompatible delivery mechanisms for the practical usefulness of RNA-based cancer therapies.