Research on the field of metal complexes for the treatment of cancer diseases has attracted increasing interest due to the urgency in finding more efficient and selective treatments. Owing to their wide structural diversity, organometallic complexes appear as potential alternatives to the design of new anticancer candidates. Herein, we review recent progress in our work toward the development of new drugs based on Ru(II)- and Fe(II)-cyclopentadienyl scaffolds. Their design and chemical properties are reviewed and correlated with their biological effects, in particular the key role that coligands play in the overall behavior of the complex.