The company, owned by Genting Singapore Ltd, did not disclose how many jobs will be lost, but the local Straits Times newspaper said the cuts were "significant".
A spokesperson for Resorts World Sentosa said the firm had over 7,000 full-time employees at the end of 2019, but declined to comment on its current employment level. The Genting Singapore website says RWS is one of Singapore's largest employers.
Resorts World Sentosa's facilities, spread over 49 hectares, encompass a hotel, a casino and a Universal Studios theme park among other attractions.
"We have made the difficult decision to implement a one-off workforce rationalisation," it said in a statement.
A handful of staff trudging past mostly quiet restaurants outside the entrance to the casino on Wednesday afternoon told Reuters they had been called in to meet with the human resources department.
Singapore's economy plunged into recession in the second quarter, shrinking a record 41% from the previous quarter, data showed on Tuesday, putting it on track for its deepest slump ever.
The tourism industry, which contributes about 4% to the economy, has been one of the worst affected sectors due to travel restrictions and a lockdown that lasted more than two months to curb the spread of COVID-19.
Across the causeway, casino operator Genting Malaysia was cutting 3,000 jobs, or about 15% of its workforce, media reported last month. Genting Malaysia did not respond to a request for comment.
Genting Singapore and Genting Malaysia are part of Malaysian conglomerate Genting Berhad.
"COVID-19 pandemic's impact on the tourism industry is unprecedented, immediate, and immense," Singapore's National Trades Union Congress said in a statement on the job cuts.
It added that it was working with Resorts World Sentosa on compensation terms, and would help affected employees with training and finding new jobs.
Just last year the company announced it would invest about S$4.5 billion ($3.2 billion) to expand its tourist attractions in the city-state.
(Reporting by Aradhana Aravindan, John Geddie and Edgar Su in Singapore; Additional reporting by Liz Lee in Kuala Lumpur; Editing by Edwina Gibbs and Kim Coghill)