A subset of castration-resistant prostate cancers (CRPC) progress to a neuroendocrine (NE) subtype (NEPC), which is characterised by rapid progression, limited therapeutic options, and poor clinical outcomes. The NE lineage transformation from AR-dependent luminal-like tumours to an AR-independent NEPC state is driven by genetic and epigenetic alterations; however, the role of 3D chromatin organisation in this lineage switch remains poorly understood. Here, we uncover a critical role for 3D chromatin organisation in NEPC lineage plasticity, which is partially recapitulated in NE-like cells undergoing transformation. NE-like cells (MR42D) retain AR activity and exhibit increased chromatin accessibility at distal regulatory elements enriched for the pioneer factor FOXA1 and key prostate lineage transcription factor HOXB13. In contrast, fully transformed NEPC cells (NCI-H660) lose AR activity and accessibility at luminal-associated androgen response elements (ARE, GRE), while gaining accessibility at sites bound by the pioneer factor FOXA2 and the neural transcription factor NKX2-2. Hi-C profiling demonstrates that NE-specific open chromatin regions engage in long-range 3D chromatin interactions to directly modulate oncogenic gene expression, including neuronal developmental processes such as dendrite morphogenesis, axon guidance, and neuron cell-cell adhesion. At the FOXA2 locus, we identified distal open chromatin regions enriched for NEPC-specific 3D chromatin interactions that were associated with increased FOXA2 expression. Furthermore, pharmacological inhibition of chromatin remodelling using the SWI/SNF inhibitor FHD-286 disrupted NE-associated gene expression and suppressed cell proliferation in vitro. Taken together, our findings establish 3D chromatin remodelling as a key driver of luminal-to-neuroendocrine plasticity in prostate cancer and highlight promising therapeutic strategies to mitigate the NEPC state.