Methods, apparatus, systems and articles of manufacture are disclosed to initialize enclaves on target processors. An example apparatus includes an image file retriever to retrieve configuration parameters associated with an enclave file, and an address space manager to calculate a minimum virtual address space value for an enclave image layout based on the configuration parameters, and generate an optimized enclave image layout to allow enclave image execution on unknown target processor types by multiplying the minimum address space value with a virtual address factor to determine an optimized virtual address space value for the optimized enclave image layout.