Aneuploidy and complex genomic rearrangements play critical roles in cancer evolution. These events, including chromothripsis, chromoplexy, and extrachromosomal DNA (ecDNA), significantly impact gene expression and tumor fitness. Large genomic alterations, such as copy number variations (CNAs), whole-genome duplications (WGDs), and structural variants (SVs), are driven by physical factors and selective pressures. Aneuploidy, caused by chromosomal instability (CIN), is a common feature in cancers, often linked to mutations in genes like TP53. WGDs, which double the genome, are associated with increased CIN and can enhance tolerance to aneuploidy. Structural variants, including translocations and inversions, contribute to oncogene activation and therapeutic resistance. ecDNA, formed from chromothripsis fragments, can amplify oncogenes and promote drug resistance. Complex rearrangements, such as chromothripsis and BFB cycles, generate oncogenic fusions and drive tumor progression. These events are often early in tumor evolution and can be influenced by selective pressures, including cancer therapies. Understanding the interplay between physical and selective factors is essential for elucidating cancer development and improving therapeutic strategies. Future research should focus on integrating genomic and computational approaches to better characterize these events and their roles in tumor evolution.Aneuploidy and complex genomic rearrangements play critical roles in cancer evolution. These events, including chromothripsis, chromoplexy, and extrachromosomal DNA (ecDNA), significantly impact gene expression and tumor fitness. Large genomic alterations, such as copy number variations (CNAs), whole-genome duplications (WGDs), and structural variants (SVs), are driven by physical factors and selective pressures. Aneuploidy, caused by chromosomal instability (CIN), is a common feature in cancers, often linked to mutations in genes like TP53. WGDs, which double the genome, are associated with increased CIN and can enhance tolerance to aneuploidy. Structural variants, including translocations and inversions, contribute to oncogene activation and therapeutic resistance. ecDNA, formed from chromothripsis fragments, can amplify oncogenes and promote drug resistance. Complex rearrangements, such as chromothripsis and BFB cycles, generate oncogenic fusions and drive tumor progression. These events are often early in tumor evolution and can be influenced by selective pressures, including cancer therapies. Understanding the interplay between physical and selective factors is essential for elucidating cancer development and improving therapeutic strategies. Future research should focus on integrating genomic and computational approaches to better characterize these events and their roles in tumor evolution.