While .NET is CPU ISA-independent, once it is JITed it becomes ISA-dependented and it is essential this matches the ISA CPython uses
The NET Common Language Runtime is Instruction Set Architecture (ISA)-indepenedent, i.e., it can run on different CPUs. Just before a piece is executed it will be compiled automatically by the CLR (JITed). On the Windows platform this compilation can happen to either the old x86 32 bit code or to newer AMD64 (which is also supported by Intel) 64bit code. The target ISA must match the architecture of the Python interpreter which is being used in an embedded setting! In Visual Studio you can use the “CPU Target” configuration option to set this – see this StackOverflow explanation.