Disclosed herein are systems and methods for multi-architecture computing. For example, in some embodiments, a computing device may include: a processor system including at least one first processing core having a first instruction set architecture (ISA), and at least one second processing core having a second ISA different from the first ISA; and a memory device coupled to the processor system, wherein the memory device has stored thereon a first binary representation of a program for the first ISA and a second binary representation of the program for the second ISA, and the memory device has stored thereon data for the program having an in-memory representation compatible with both the first ISA and the second ISA.