<p>The cell nucleus, recognized as the largest and most rigid organelle within eukaryotic cells, serves a pivotal function in transcriptional regulation and displays remarkable adaptability to both intracellular and extracellular mechanical forces. These forces are transmitted through the cytoskeleton and the linker of the nucleoskeleton and cytoskeleton (LINC) complex, resulting in modifications to nuclear morphology, structure, and mechanical features. Such adaptations are essential for mechanotransduction, influencing gene expression and modulating various cellular signaling pathways. Dysregulation of nuclear proteins, particularly lamins, or mutations affecting these constituents can disturb nuclear mechanics and cytoskeletal organization, thereby contributing to the pathogenesis of several diseases, including cardiovascular disorders, aging and cancer. Furthermore, nuclear architecture plays an integral role in mechanoregulation by transmitting mechanical strains and osmotic stresses to the genome, effectively linking structural remodeling with transcriptional regulation and cellular differentiation. Here, we present a comprehensive examination of nuclear mechanics, with a specific emphasis on the mechanical properties of the nucleus, the pathways involved in mechanotransduction, methodologies for assessing nuclear mechanical properties, and potential applications within the field of medicine.</p> Graphical Abstract <p></p>