Cancer is an evolutionary process driven by clonal expansion, genetic diversification, and selection within tissue ecosystems. Therapeutic interventions can eliminate cancer clones but may also select for resistant variants, highlighting the Darwinian nature of cancer. Understanding cancer as an evolutionary system is crucial for effective treatment. Cancer evolves over time with complex genetic diversity and clonal architecture. Mutations can be drivers or passengers, with drivers contributing to malignancy. Clonal evolution involves interactions between driver, passenger, and mutator lesions, as well as changes in the microenvironment. Cancer cells adapt to their environment, and evolutionary principles explain therapeutic resistance. Clonal competition and selection are key factors in cancer progression. The tumor microenvironment influences cancer cell evolution, and genetic diversity within tumors can lead to therapeutic resistance. Cancer genomics reveals the complexity of tumor genomes, with many mutations being neutral. Sub-clonal diversity is a key factor in therapeutic failure. Cancer stem cells, with their self-renewal properties, are critical in clonal evolution. Therapeutic strategies must consider the evolutionary dynamics of cancer, including the need for targeted therapies and ecological approaches. Understanding cancer as an evolutionary process can lead to more effective treatments and prevention strategies.Cancer is an evolutionary process driven by clonal expansion, genetic diversification, and selection within tissue ecosystems. Therapeutic interventions can eliminate cancer clones but may also select for resistant variants, highlighting the Darwinian nature of cancer. Understanding cancer as an evolutionary system is crucial for effective treatment. Cancer evolves over time with complex genetic diversity and clonal architecture. Mutations can be drivers or passengers, with drivers contributing to malignancy. Clonal evolution involves interactions between driver, passenger, and mutator lesions, as well as changes in the microenvironment. Cancer cells adapt to their environment, and evolutionary principles explain therapeutic resistance. Clonal competition and selection are key factors in cancer progression. The tumor microenvironment influences cancer cell evolution, and genetic diversity within tumors can lead to therapeutic resistance. Cancer genomics reveals the complexity of tumor genomes, with many mutations being neutral. Sub-clonal diversity is a key factor in therapeutic failure. Cancer stem cells, with their self-renewal properties, are critical in clonal evolution. Therapeutic strategies must consider the evolutionary dynamics of cancer, including the need for targeted therapies and ecological approaches. Understanding cancer as an evolutionary process can lead to more effective treatments and prevention strategies.