<p>Migraine is a complex neurological disorder characterized by recurrent unilateral headaches. Its pathophysiology has been associated with inflammatory processes, with <i>TNF-α</i>, a pro-inflammatory cytokine, being one such factor implicated in various neurological conditions, including migraine. This study aimed to evaluate the association between the <i>TNF-α</i> -308 G &gt; A polymorphism and migraine risk by integrating both a case–control investigation and a meta-analysis to enhance statistical power and reliability. The investigation commenced with a case–control study in the Jammu region of North India, conducted in accordance with STROBE guidelines. To enhance statistical power and reliability, a meta-analysis of independent studies was performed, followed by Trial Sequential Analysis to verify sample size adequacy. First, the case–control study showed that there was no significant association between -308 G &gt; A and overall migraine risk across various genetic models (allele: 0.80 [0.58–1.11], <i>p</i> = 0.193) in the Jammu population. Although the migraine with aura subgroup showed marginal significance in the allelic model (<i>p</i> = 0.02), this association was not supported after adjustment (<i>p</i> = 0.14). Similarly, the meta-analysis revealed no significant association between the polymorphism and overall migraine (allele: 1.21 [0.92–1.58], <i>p</i> = 0.16) or its two clinical subtypes, migraine with aura and without aura. However, when stratified by ethnicity, a significant association was identified in African populations, while no such association was observed in Asian or Caucasian groups. This study underscores the importance of combining case–control data with meta-analysis to strengthen genetic association findings. Future research should focus on larger, multi-ethnic cohorts to validate these findings and improve generalizability.</p> Graphical abstract <p></p>