Can a regtest bitcoind node use SignRawTransactionWithKey + prevtxs for a mainnet raw transaction? I want to know if a regtest nnode can sign a raw mainnet transaction with the signrawtransactionwithkey rpc provided that I pass the correct keys and prevtxs as the regtest node will not be aware of them?
No, you will get an Invalid private key error. Note that if you use a correct-network private key but it is the wrong key to sign the input you provide you get a different error: Unable to sign input, invalid stack size (possibly missing key)
The base58 prefix is checked against a constant value that is different for each network (main, regtest, etc)
const std::vector&lt;unsigned char&gt;&amp; privkey_prefix =
    Params().Base58Prefix(CChainParams::SECRET_KEY);

https://github.com/bitcoin/bitcoin/blob/master/src/key_io.cpp#L132-L148