Migraine and other headache disorders are among the most common and disabling brain conditions worldwide. According to the Global Burden of Disease (GBD) 2023 study, more than three billion people are affected, making these disorders one of the leading causes of years lived with disability across all ages. Yet, despite this vast burden, migraine and headache disorders remain outside most non-communicable disease (NCD) strategies and are excluded from universal health care (UHC). This neglect is shocking to say the least. The imbalance between burden and investment is profound. Research activity and funding for migraine remain disproportionately low compared with other major non-communicable diseases, even though the human and economic costs are enormous. This underinvestment fuels an ongoing cycle of underdiagnosis, trial-and-error care, stigma, and lost productivity. Health systems in low- and middle-income countries (LMICs) are particularly affected, with scarce resources and limited structured access to prevention and rehabilitation. We propose the Systems Neuroscience Toolbox for Migraine (SNTBM), a globally applicable framework that integrates functional vision and cognitive tests, systemic immune-inflammatory biomarkers, and tiered rehabilitation strategies. Core components include brief, tablet-based attention and eye–hand coordination tasks, contrast sensitivity and pattern-glare checks, tele-retinal photography for neurovascular health with the help of local Optometry services, and basic blood indices such as neutrophil-to-lymphocyte ratio, serial systemic immune inflammatory indices and C-reactive protein. These low-cost, widely available objective measures, paired with patient-reported outcomes and migraine diaries, generate phase-sensitive profiles that can guide personalized care. The SNTBM is designed for scalability, equity, and alignment with UHC. It operates through a tiered approach: Tier 1 focuses on self-management with education, sleep hygiene, exercise, and mind–body strategies such as yoga and mindfulness; Tier 2 equips primary care teams to deliver structured testing and stepped preventive therapy; and Tier 3 offers specialist care for chronic, refractory, or complex cases with access to advanced treatments where available. Beyond immediate clinical use, the toolbox reframes migraine as a measurable systems disorder and accelerates biomarker discovery for translational research. This initiative builds on more than 40 years of experimental neurobiology and psychophysics research from the Crewther laboratory, combined with over two decades of frontline clinical practice by Wijeratne in rural Sri Lanka and disadvantaged suburbs of Australia. Crucially, the toolbox has been designed in strong partnership with hundreds of people living with migraine in both Sri Lanka and Australia, ensuring that it reflects real-world priorities, cultural contexts, and patient experience. The SNTB thus offers not only scientific rigor but also a new hope for the billions worldwide who live with migraine and headache disorders.