<p>The genomic investigation of toxigenic cyanobacteria reveals unique features of potential genes, proteins, and genomic regions associated with varied functions critical for their survival and stress tolerance. Cyanobacteria are prevalent photoautotrophic microorganisms forming harmful blooms in aquatic environments, with significant public health and ecological implications. Despite the availability of complete genome sequences, the stress genomics of these harmful cyanobacteria remains understudied. This review highlights the genomic “arsenal” of these resilient species, emphasizing their stress adaptation mechanisms and potential vulnerabilities. Understanding this molecular basis is essential for developing targeted strategies to mitigate their impact. The insights gained from the genomic analysis could be leveraged to express unexploited stress-related genes for enhanced stress tolerance in industrial applications. Additionally, the review underscores the importance of redirecting research focus towards the functional genomics of bloom-forming strains to uncover novel pathways and strategies for their selective eradication and to improve the productivity of beneficial cyanobacterial strains under fluctuating environmental conditions. Finally, this review is an effort towards creating an important genomic resource for such toxic cyanobacteria.</p>