What leads you to that conclusion ?
There are plenty of smaller European states that seem to manage just fine. It's true that there are areas of Wales which are among the most deprived in the UK, but they're by no means the most deprived. Then again there are areas, particularly along the M4 corridor which are doing very nicely indeed.
Wales has benefited from EU funding but there is some debate as to whether Wales is a net recipient of EU funding. If UK per capita contributions are considered then Wales may be a net contributor, reports on other studies indicate that it's a net recipient.
https://www.walesonline.co.uk/news/politics/report-claims-wales-gets-245m-11375402
Of course, if an independent Wales was in the EU but England wasn't and was operating on significantly different terms with the EU than it currently does (WTO terms or limited trade deal) then that would have profound effects on the Welsh economy. Some sectors could benefit from work moving from England to Wales as EU companies review their suppliers and other sectors could be hit.