The field of gene editing has witnessed remarkable advancements with the emergence of epigenetic modifications and CRISPR-Cas9 technology. Epigenetic modifications, such as DNA methylation and histone modifications, play a critical role in gene regulation and have been implicated in various diseases, including cancer and genetic disorders. The advent of CRISPR-Cas9, a versatile gene-editing tool, has revolutionized the field by enabling precise and targeted modifications of the genome. This chapter provides an overview of epigenetic modifications and their role in gene regulation, as well as an in-depth exploration of CRISPR-Cas9 and its potential applications in gene editing. We discuss the ability of CRISPR-Cas9 to target epigenetic modifications, such as DNA demethylation and histone modification, and highlight the potential of combining epigenetic modifications with CRISPR-Cas9 for precise gene regulation. Furthermore, we delve into the opportunities and challenges presented by epigenetic modifications and CRISPR-Cas9 in disease treatment, including their applications in cancer therapy and genetic disorder correction. The chapter also examines recent studies and clinical trials utilizing CRISPR-Cas9 for gene editing in disease treatment, providing insights into the current state of the field. We address the challenges and limitations associated with CRISPR-Cas9, such as off-target effects and delivery challenges, and discuss the ethical considerations surrounding gene editing in humans. Finally, we outline future directions and the potential of epigenetic modifications and CRISPR-Cas9 in gene editing and disease treatment. This comprehensive exploration of epigenetic modifications and CRISPR-Cas9 underscores the opportunities and challenges in harnessing these technologies for precise and personalized gene editing, paving the way for transformative advancements in molecular biology and medicine.