In canine solid tumors, genetic alterations are crucial for initiating and advancing tumor growth, leading to modifications in the originating tissue and shaping the tumor’s developmental course. Structural variants, including inversions, deletions, and translocations, are hallmarks of most cancer genomes and are causatively linked to tumorigenesis. Histopathology was used to confirm tumor type, while structural genomic alterations were identified through whole-genome sequencing. The examination of 4 tumors and 52 normal whole-genome sequences enabled a precise exploration of the genetic foundations of solid tumor biology, particularly the pattern of somatic structural variation. Structural variants in tumor samples were predominantly found in genes involved in the RTK–Ras–MEK–ERK signaling pathway, as well as in those regulating apoptosis and cell survival. Among the structural variants discovered, the detection of STARD4 in the solid tumor group, which is related to cholesterol regulation, indicates a potential common pathway in tumorigenesis. This research highlights the genetic intricacy of tumors and underscores the importance of personalized strategies for diagnosis and prognosis, employing comprehensive genetic profiling.