Heat shock protein 90 (Hsp90) performs functions in cellular activities together with other signaling pathways. Hsp90 is evolutionarily conserved and universally articulated as a human cancer-causing agent involved in lung cancer and breast cancer followed by colon and rectum cancers. It has emerged as an effective drug candidate, and inhibition may affect several signaling pathways associated with cancer spread. Therefore, in-silico approaches, molecular docking, molecular dynamics simulation, and binding free energy calculations were applied to create insights into the inhibition mechanism against Hsp90 to identify new cancer therapeutic drugs. Top-docked Hsp90-inhibitor complexes with their analogues were selected as the best complexes based on the GOLD fitness score and orientation. The significant interaction of Hsp90 inhibitors and their analogues were observed to be bound with active site residues as well as residing within the same cavity region. System stability factors RMSD, RMSF, beta-factor, and radius of gyration were analyzed for top-docked complexes and ensure strong binding interaction between inhibitors and the Hsp90 cavity. Cavity bound inhibitors were found to retain consistent hydrogen bonding during the simulation. The radial distribution function (RDF) illustrated that interacting active site residues drive the binding and stability of the inhibitors. Similarly, the axial frequency distribution, which is an indigenously developed analytical tool, produced noteworthy knowledge of the hydrogen-bonding pattern. Results yielded new insights into the design of cancer therapeutic drugs against Hsp90. This finding suggests that under trial Hsp90 inhibitors MPC-3100 could be a potential starting point into the development of potential anticancer agents with the possibility of future directions for the improvement of early existing Hsp90 inhibitors CNF-2024 and SNX-5422 as an anticancer agent.