Abstract BACKGROUND Adamantinomatous Craniopharyngiomas (ACPs) are rare tumors arising from the remnants of the craniopharyngeal duct epithelium. Their diagnosis poses unique challenges, often resulting in delayed identification due to their slow growth and nonspecific symptoms. Additionally, the prolonged overall survival (OS) is overshadowed by a substantial recurrence rate and late consequences, posing significant challenges, and impairing the patient’s quality of life (QoL). Recent advancements in understanding ACP’s genomic, transcriptomic, and proteomic aspects underscore the need for innovative treatments to mitigate these long-term consequences. METHODS We conducted an in-depth literature review, focusing on large clinical trials and major publications in ACP to provide a comprehensive perspective on the challenges in the diagnosis, treatment, and molecular aspects of pediatric ACP. RESULTS ACP’s clinical presentation involves increased intracranial pressure, endocrine abnormalities, and visual impairments. Despite their low-grade classification, ACPs exhibit aggressive clinical behavior, often invading or adhering to adjacent tissues, particularly critical neurovascular structures. Imaging techniques, including CT and MRI with a focus on hypothalamic involvement, play a crucial role in diagnosis, pre-operative evaluation, and surgical planning. Multidisciplinary approaches are essential for developing tailored treatment strategies. Neurosurgical management and radiotherapy, particularly proton therapy, are the primary therapeutic modalities. The molecular landscape reveals intricate and complex mechanisms and include the upregulation of the Wingless (WNT) signaling pathway driven by CTNNB1 mutations, along with involvement of inflammatory, programmed cell death, and the MAPK/ERK pathways. Ongoing trials exploring targeted therapies may play a pivotal role in refining treatment strategies and improving outcomes. CONCLUSIONS Navigating the complexities of ACP requires a multidisciplinary approach. Advances in diagnostics, surgical strategies, and targeted therapies, informed by molecular insights, offer promising avenues for improving outcomes and QoL. Ongoing collaborative efforts and participation in clinical trials are vital for refining treatment strategies and advancing the understanding of this challenging condition.