The main difference between Microsoft 365 and Office 2021 Professional lies in the purchase method and features offered. Microsoft 365 is a subscription service that is constantly updated with the latest features along with additional benefits such as significant OneDrive storage.
Office 2021 Professional, on the other hand, is a one-time purchase that gives users access to the classic Office applications with all security and application updates. As such, you can save a lot of money on subscriptions. You will not have additional OneDrive storage but there are alternatives for this.