The study, carried out by NatWest and data company Beauhurst, analysed growth across innovation, profit, headcount and turnover among mid-market firms nationwide.
Reading ranked 22nd and stood out for its research-driven businesses.
Manchester was placed second behind London thanks to its thriving creative and digital sectors, fuelled by MediaCityUK and a flourishing start-up scene.
Leeds came third, having built a reputation in health technology to complement its long-established financial services sector, strengthened by close ties to NHS Digital and leading hospitals.
While London remains the largest centre for profit, headcount and turnover in the mid-market, the report reveals other areas of the UK are increasingly standing out for their innovation.
Smaller authorities also made the list, with Slough and Telford & Wrekin both highlighted as growth hotspots.
Swindon has also emerged as one of the nation’s leading climate technology hubs, thanks to its cluster of renewable energy and clean-tech firms.
Andy Gray, managing director of commercial mid-market at NatWest said: “The UK’s economic story is no longer written only in its biggest cities.
“Across the country, mid-sized businesses are scaling up, investing in people and creating high-quality jobs.
“These boom regions demonstrate that entrepreneurial energy and economic resilience can flourish anywhere.”
Buckinghamshire was placed as highly as sixth, while Reading in Berkshire placed 22nd, rounding off the Thames Valley inclusion.
