Solid tumors collectively drive the global cancer burden, with profound molecular heterogeneity demanding precision and molecularly informed management. Advances in sequencing technologies have established molecular taxonomy as a cornerstone of clinical oncology, progressively superseding traditional histopathological classifications. Sanger sequencing remains the gold standard for validating guideline mandated actionable variants. Next-generation sequencing (NGS) has revolutionized early cancer detection through liquid biopsy applications and enabled the reclassification of diagnostically challenging tumor subtypes. Emerging long-read platforms offer unique capabilities to resolve complex genomic rearrangements, structural variants, and therapy-induced epigenetic remodeling. Consequently, therapeutic strategies are shifting from organ-centric approaches to mutation-specific interventions, exemplified by non-small-cell lung cancer, where molecular stratification drives substantial improvements in treatment response. Nevertheless, temporal tumor heterogeneity, biological contamination, and computational limitations highlight the urgent need for robust, integrated verification systems. Collectively, this evolution positions sequencing as the operational backbone of adaptive precision oncology across solid tumors. Here, we synthesize our laboratory findings with the current literature to comprehensively review the diagnostic, therapeutic, and prognostic applications of first- through fourth-generation sequencing technologies and discuss future directions in this rapidly evolving field.