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Global cancer incidence and death are expected to increase to 28.4 million cases by 2040, despite efforts to understand cancer biology better and to improve its diagnosis and therapy [1]. Inappropriate therapeutic regimens and tumor recurrence due to the development of drug resistance are two major clinical challenges impacting poor patient outcomes [2]. Over the last few decades, the marine environment has become an important source of molecules with potent anticancer properties, exhibiting unusual chemical features and mechanisms of action. Twelve of seventeen drugs of marine origin approved by regulatory entities are used against cancer, and thirty-four of forty compounds in the marine pharmaceuticals pipeline indicate “cancer therapy”[3]. The Special Issue “Marine Natural Products as Anticancer Agents 2.0”(https://www. mdpi. com/journal/marinedrugs/special_issues/AnticancerAgents2, accessed on 11 April 2023) gathered eleven publications, including two reviews and nine research articles, about the anticancer activities of marine natural and/or derived products on in vitro 2D and 3D cellular models, and/or in vivo models of colorectal, breast, lung, myeloma, liver, leukemia, and melanoma cancers. Marine natural and/or derived products addressed herein were obtained from sponges, seaweeds, fungi, and soft corals. Those compounds exhibit great chemical diversity, such as terpenes, alkaloids, fatty acids, phenolics, polysaccharides, and peptides. Some compounds are halogenated. It is also relevant to highlight the key importance of “nature power creativity”, evidenced in this Special Issue as a supplier of scaffolds for the …