Rising inequality in advanced economies is a global challenge and a major factor behind the current wave of geo-political disruption. It has been driven by a polarisation between regions which are creating wealth and benefitting from wealth creation, and those left behind. This justifies a wholesale reinvention of these capitalist systems. Focusing on the UK example, this Element presents evidence of systemic failure, with low productivity alongside higher levels of deprivation in city-regions outside of London. Comparisons show that this is a challenge for other advanced economies. Long term underinvestment in regions has reached a tipping point a centralised governments channels public resources into London, rather than 'levelling-up'. This Element proposes several 'intelligent interventions,' emphasising the need for stronger and more inclusive regional innovation systems, built on a deeper understanding of sustainable local growth pathways. Although based primarily on the UK experience, these policies are relevant beyond the UK context.