Cancer treatment is shifting from generic cytotoxic drugs to personalized approaches based on individual tumor molecular features. New paradigms focus on patient-specific factors like genomic alterations, signaling pathway activities, and gene expression. Precision oncology aims to provide the most effective treatment while minimizing exposure to ineffective therapies and reducing side effects. This approach could revolutionize cancer care, moving from reactive to proactive and predictive strategies. The article reviews past and current precision oncology approaches, highlighting their strengths and limitations, and speculates on emerging methodologies to address existing challenges.