<p>Iron is an essential component for the development of cells and metabolism. Understanding metal-associated proteins and their role in cancer development is crucial, as iron’s critical role in cancer development becomes increasingly acknowledged. Since iron and mutations are essential to cancer development and progression, the current study investigates iron-binding proteins (IBPs) in the mutational landscape of cancer. Using bioinformatics approaches we identified and classified 57 IBPs from the known 810 cancer-related proteins. These IBPs perform diverse functions as enzymes, transporters, and signaling proteins. Out of Eighteen metastasis-associated IBPs, two proteins, namely P08253 (MMP-2, which degrades components of the extracellular matrix and plays a role in cellular migration) and P08183 (ABCB-1 ATP binding cassette transporters), have been observed as having high and low expression profiles in most of the tumour types, respectively. Iron binding sites in most of the mutation states of all the shortlisted 18 metastasis-associated IBPs, including MMP-2 and ABCB-1, have been changed compared to wild-type states. To further investigate the effect of mutations, we performed molecular dynamics simulations, which demonstrate that these mutations impact the protein structure, function, and binding affinity of the small molecules. This highlighted that the mutations in IBPs not only disrupt iron interaction but also alter the therapeutic molecules’ activity.</p>