Multi-domain creation and isolation within a heterogeneous System-on-Chip (SoC) may include receiving a hardware description file specifying a plurality of processors and a plurality of hardware resources available within a heterogeneous SoC and creating, using computer hardware, a plurality of domains for the heterogeneous SoC, wherein each domain includes a processor selected from the plurality of processors and a hardware resource selected from the plurality of hardware resources. The method may include assigning, using the computer hardware, an operating system to each domain and generating, using the computer hardware, a platform that is configured to implement the plurality of domains within the heterogeneous SoC.