Italy is a country marked by severe structural and economic contrasts across different areas: Italian regions differ greatly in terms of demographic patterns, economic performance, well-being, and institutional quality. The North-South divide has been a distinctive feature of Italian economic development since the country’s political unification in 1861. The trend of divergence appears to be reinforced by 21st century transformation pressures which have hit Italian regions that display different levels of preparedness. Indeed, the disparity map shows that Italy can be differentiated into four spatial types. Better place-sensitive territorial development policies are needed in order to find a solution to the longstanding differences between North and South: policies focused on providing opportunities for people living in the Southern regions and on tapping into untapped potential.