The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA changes, often precede genetic mutations and are critical in cancer progression. In this study, we explore how liquid biopsy, combined with epigenetic markers, can provide early detection of lung cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges of targeting epigenetic regulators, which could disrupt cellular balance if overexploited, and the need for maintaining key gene expressions in therapeutic applications. This review highlights the promise and challenges of using liquid biopsy and epigenetic markers for early-stage lung cancer diagnosis, with a focus on optimizing treatment strategies for personalized and precision medicine.