Migraine headache (MH) and cluster headache (CH) are debilitating primary headache disorders that impose a significant global burden. While they share certain clinical features, such as unilateral pain and autonomic dysfunction, their underlying pathophysiological mechanisms remain distinct. Advances in the understanding of neurophysiological features, such as neuroimaging and biomarker research, have provided critical insights into both their overlapping and divergent characteristics. Neurophysiological research has revealed differences in nociceptive processing, cortical excitability, and sensory integration, underscoring the complexity of these conditions. Neuroimaging studies reveal common activation patterns within pain-processing networks, including the trigeminal system and hypothalamus, while highlighting key differences, such as hypothalamic hyperactivity in CH and cortical alterations in MH. Additionally, biomarker research has identified shared elements, including elevated calcitonin gene-related peptide (CGRP), yet distinct variations in its regulation and genetic predispositions. Genome-wide association studies have further elucidated the genetic architecture of these disorders, uncovering susceptibility loci that reinforces their unique yet occasionally intersecting genetic foundations. These multifield advancements not only enhance the understanding of MH and CH pathophysiology but also pave the way for improved diagnostic precision, personalized therapeutic strategies, and future research.