The emergence of precision medicine marks a transformative shift in cancer care, moving away from conventional, generalized therapeutic strategies toward a more individualized approach that considers the unique genetic, molecular, and environmental context of each patient. This chapter provides an in-depth exploration of the foundational principles and concepts of precision oncology. It begins with a discussion of the historical evolution of cancer treatment and the limitations of traditional models, setting the stage for the rise of personalized medicine. Core components such as genomic profiling, biomarker discovery, molecular diagnostics, and the role of predictive and prognostic indicators are examined in detail. Additionally, this chapter highlights the critical role of technologies such as NGS, liquid biopsies, and artificial intelligence in driving forward the field. Case examples of successful targeted therapies (e.g., EGFR inhibitors, ALK inhibitors, PARP inhibitors) are presented to illustrate clinical applications. The chapter also addresses the major challenges facing precision medicine, including tumor heterogeneity, drug resistance, cost, data interpretation, and ethical concerns and discusses future directions aimed at improving accessibility, refining predictive models, and integrating multi-omics data for holistic patient care. By synthesizing current knowledge and emerging trends, this chapter serves as a foundational resource for understanding how precision medicine is reshaping the diagnosis, treatment, and prevention of cancer.