Difference between the .NET API and the .COM API.?

There's a difference in capabilities available through Eikon COM and .NET APIs. E.g. in addition to real-time market data Eikon COM APIs can retrieve fundamental and reference data, which Eikon .NET APIs cannot. Eikon .NET APIs can retrieve the depth and breadth of market data history, which is not available through Eikon COM APIs. But for real-time market data retrieval both APIs provide similar capabilities, so the difference is mainly in technology. Both APIs can be used in custom .NET applications. Eikon .NET APIs provide a more modern interface and arguably are easier to use in .NET. Eikon COM APIs on the other hand can be easily used in VBA.
Both Eikon COM and .NET APIs are considered legacy and are not being enhanced. They're in care & maintenance. Our strategic data retrieval APIs for Eikon are Eikon Data APIs. The capabilities of these strategic APIs are not yet on par with legacy Eikon APIs, which is why we're not looking to retire the legacy APIs yet. At the moment Eikon Data APIs can only retrieve real-time market data as snapshot. We're starting EAP for the new version of the API, which provides capability to subscribe to streaming market data.
It's possible to use Eikon COM APIs in Python, but it's cumbersome and I wouldn't recommend it. Given that we're very close to introducing streaming capability into Eikon Data APIs, I would suggest waiting for that. Perhaps join the EAP if you're interested.
I have used Eikon .NET APIs in Java in one project through JNI using JIN4NET to bridge Java and .NET. It works and in lieu of any alternative it's a viable approach. But again it's rather cumbersome and not straightforward. In future we'll be introducing Java version of Eikon Data APIs, but there's no definitive timeframe for that yet.