This paper provides a System-of-Systems (SoS) perspective for integrated design and evaluation of an Information Fusion System (IFS). IFS is comprised of distributed and heterogeneous systems that accomplish low-level and high-level information fusion (LLIF and HLIF) functionality. LLIF and HLIF functions are developed independent from one another but require collaboration to achieve the IFS mission objectives. The distribution and heterogeneity of systems, in addition to the multiplicity of LLIF and HLIF functions, creates an extensively large design space for the IFS. We apply a SoS engineering architecting process to obtain integrated architectures of IFS and propose guidelines to constrain an otherwise infinite design space of Information Fusion System-of-Systems (IF-SoS). Furthermore, we elaborate a multi-agent system modeling approach and pair it with Design of Experiments for objective evaluation of the IF-SoS design space. The statistical analysis, based on analysis of variance (ANOVA) and Tukey Honest Significant Difference (HSD) Range Tests, quantifies the impact of interactions between LLIF and HLIF design considerations on the IF-SoS performance. Furthermore, statistical evidence is provided to demonstrate that the interactions among JDL levels, in particular between LLIF and HLIF, are the most significant design considerations for fusion performance which necessitate an integrated design and evaluation of LLIF and HLIF—a manifestation of the SoS perspective for the IFS.