Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumours with variable biology, clinical behaviour, and prognosis. Traditional classification based on differentiation and proliferation provides valuable but incomplete insights into disease heterogeneity. Recent genomic and epigenetic studies have identified key molecular drivers—including MEN1, DAXX, ATRX, and components of the mTOR and MAPK pathways—revealing distinct biological subtypes with prognostic and therapeutic implications. Advances in next-generation sequencing have uncovered actionable mutations, DNA repair defects, and emerging biomarkers such as alternative lengthening of telomeres and copy-number variants. Although routine molecular testing is not yet standard in all centres, its integration is reshaping diagnosis, prognostication, and access to targeted therapies. Molecular profiling promises a more precise, biologically driven framework for the management of NENs.