<p>A variety of microorganisms are able to tolerate metals that are prevalent in the environment. In the current study, insights into heavy metal tolerance in the tropical marine Actinobacterium – <i>Nocardiopsis dassonvillei</i> NCIM 5124 are presented. The organism was able to tolerate metals in the order Cd²⁺ &gt; Cr³⁺ &gt; Cu²⁺ = Ni²⁺ (1.0 to 5.0 mM) and Cr⁶⁺ &gt; Pb²⁺ &gt; Hg²⁺ (0.1 to 0.5 mM). Two metals Cd²⁺ and Cr⁶⁺ were considered during further studies. Field emission scanning electron microscope observations displayed a decrease in filament width (compared to control samples) and revealed metal deposits on the cell surfaces. Signature peaks observed in the energy dispersive X- ray spectra confirmed the metal-microbe interactions. The whole genome sequence revealed the presence of efflux transporters, redox/detoxifying enzymes, regulatory elements, metal specific genes, and siderophore complexes that may be relevant in metal tolerance. Transcriptome analysis in the presence of Cd²⁺ and Cr⁶⁺ ions revealed a differential response. With Cd²⁺ ions, genes encoding metalloregulator ArsR/SmtB family transcription factors, cation-translocating P-type ATPase, cadmium resistance transporter, MerR family transcriptional regulator were seen to be upregulated. In case of Cr⁶⁺ ions, siderophore biosynthesis related genes (IucA/IucC family, iron-siderophore complexes) and phosphate transporters among other genes were upregulated. q-PCR experiments validated the role of specific genes involved in Cd²⁺ and Cr⁶⁺ tolerance. The current study demonstrates the potential of this Actinobacterium in bioremediating heavy metal contaminated sites.</p>