Marine biodiversity covers >70% of Earth’s surface and harbors a vast array of species (>300,000 described across 34 of 36 phyla) that produce unique secondary metabolites. The marine environment has yielded a growing pipeline of anticancer leads: For example, trabectedin (from the tunicate Ecteinascidia) is an alkylating agent that binds DNA, salinosporamide A (from a marine Streptomyces) is a potent 20S proteasome inhibitor, and bryostatin-1 (from the bryozoan Bugula neritina) is a macrocyclic lactone that modulates protein kinase C. Modern omics technologies (genomics, transcriptomics, proteomics, metabolomics, and their integration) are revealing biosynthetic gene clusters in uncultured marine microbes and elucidating mechanisms of these compounds. Complementary biotechnological advances—including synthetic biology, genome editing (e.g., clustered regularly interspaced short palindromic repeats [CRISPR]), metabolic engineering, and optimized microbial fermentation—are enabling sustainable production of complex marine molecules. Similarly, nanotechnology and novel delivery systems (nanoparticles and antibodies–drug conjugates) are improving the stability and targeting of marine-derived drugs. Case studies of trabectedin, salinosporamide A (marizomib), and bryostatin-1 exemplify these themes. Key challenges remain in scalable supply, structural complexity, and clinical translation of marine compounds. Future perspectives include integrating marine pharmacology with healthomics—leveraging patient multi-omics and systems biology to guide discovery and precision use of marine-derived anticancer therapies.