The growing use of hardware accelerators in both embedded (e.g. automotive) and high-end systems (e.g. Cloud infrastructure) triggers an urgent demand for simulation frameworks that can simulate in an integrated manner all the components (i.e. CPUs, Memories, Networks, Hardware Accelerators) of a system-under-design(SuD). By utilizing such a simulator, software design can proceed in parallel with hardware development which results in the reduction of the so important time-to-market. The main problem, however, is that currently there is a shortage of such simulation frameworks; most simulators used for modeling the user applications (i.e. full-system CPU/Mem/Peripheral simulators) lack any type of support for tailor-made hardware accelerators. ACSIM framework is the first known open-source, high-performance simulator that can handle holistically system-of-systems including processors, peripherals, accelerators and networks; such an approach is, for example, very appealing for the design of Cloud Servers that incorporate FPGAs as PCI-connected accelerators. ACSIM is an extension of the COSSIM simulation framework and it integrates, in a novel and efficient way, a combined system and network simulator with a SystemC simulator, in a transparent to the end-user way.