The UN's World Intellectual Property Organization (WIPO) said the Chinese cluster had leapfrogged its Japanese rival in its 2025 Global Innovation Index.
The change at the top of the world's 100 leading innovation clusters was down to WIPO broadening the criteria to include venture capital investments to formulate the annual rankings.
The UN agency dealing with patenting and innovation previously only used patent filing and scientific publishing data to identify local concentrations of world-leading innovation activity.
"Venture capital investment activity helps capture how scientific and technological knowledge translates into start-up creation and, ultimately, new goods and services in the marketplace," WIPO said.
The agency said Shenzhen-Hong Kong-Guangzhou and Tokyo-Yokohama "make a massive contribution to global scientific publications and patenting outputs", together accounting for nearly one in five patent applications filed globally.
- Indian cities surge -
The new ranking showed that San Jose-San Francisco has now overtaken Beijing, Seoul and Shanghai-Suzhou to grab the third place.
London has shot up from 21st to eighth place, while Bengaluru has likewise jumped from 56th place to 21st on the back of venture capital deals.
"Innovation clusters form the backbone of strong national innovation ecosystems, helping to anchor and strengthen the journey from ideas to market," said WIPO chief Daren Tang.
The recalibrated rankings "highlight which clusters are turning scientific research into economic results".
Overall, the change in methodology has seen East Asian clusters drop while US clusters have made gains.
The change boosted Indian clusters, while those in the European Union -- where the venture capital markets are sometimes less vigorous than in the United States -- have tended to see a decline.
- Most innovation clusters in China -
The top 100 innovation clusters are spread across 33 economies, uniting "top universities, researchers, inventors, venture capitalists and research and development firms in driving forward breakthrough ideas", WIPO said.
By country, China for the third consecutive year led the ranking with the most clusters in the top 100, at 24, followed by the United States with 22 clusters.
WIPO said the clusters with the most innovation-intensive activity in proportion to population size were San Jose-San Francisco in the United States, followed by Britain's Cambridge.
- Top 15 -
The top 15 innovation clusters in 2025:
1: Shenzhen-Hong Kong-Guangzhou (China)
2: Tokyo-Yokohama (Japan)
3: San Jose-San Francisco (United States)
4: Beijing (China)
5: Seoul (South Korea)
6: Shanghai-Suzhou (China)
7: New York City (United States)
8: London (Britain)
9: Boston-Cambridge (United States)
10: Los Angeles (United States)
11: Osaka-Kobe-Kyoto (Japan)
12: Paris (France)
13: Hangzhou (China)
14: San Diego (United States)
15: Nanjing (China)
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