Migraine, a prevalent primary headache disorder, impacts over 1 billion individuals globally, with a prevalence of 14%. The disease burden extends across social, personal, and professional realms, ranking second among neurological disorders in disability years. Despite various therapeutic options, migraine remains underdiagnosed and undertreated worldwide. Genetic predisposition contributes significantly to migraine susceptibility. Polygenic factors and rare monogenic mutations, such as familial hemiplegic migraine, underlie its complex etiology. Neurophysiological studies reveal heightened neuronal excitability in migraine, possibly linked to genetic variations affecting synaptic function and ion channels. Comorbidities, including mood disorders, stroke, epilepsy, and sleep disturbances, are common in migraine, suggesting shared pathophysiological mechanisms. The migraine attack encompasses premonitory, aura, headache, and postdrome phases, each regulated by distinct pathogenic pathways. During the premonitory phase, intricate interactions occur among several cortical and subcortical brain regions, including the hypothalamus and brainstem nuclei involved in nociceptive processing. The trigeminovascular pathway becomes activated during the headache phase, while cortical spreading depression is responsible for migraine aura. Neuropeptides like CGRP, PACAP, and VIP play pivotal roles in migraine pathophysiology, influencing pain perception and vasodilation. Despite advances in understanding migraine mechanisms, gaps persist, hindering precise therapeutic targeting. Further research into genetic, neurophysiological, and neuropeptide aspects promises insights into migraine’s multifaceted nature, potentially paving the way for more effective treatment.