This chapter argues that cities and regions should follow strategies of “constructed advantage” to engage with the global knowledge economy. Constructed advantage strategies involve i) attraction and retention of talent – requiring business development opportunities, risk capital availability and market access as well as quality of life, ii) attraction of investment – requiring access to smart people, infrastructure, funds, technologies, markets and a complementary regulatory regime, and iii) appropriate public policy – requiring leadership and collaborations from all stakeholders. Examples are given from Canadian cities.