Phytoremediation is one of the auspicious strategies to manage heavy-metal polluted soils. Several plants act differently to accommodate this issue rather by uptake (phytoextraction), breakdown/transform (phytodegradation), emit in the atmosphere (phytovolatilization), or stabilize heavy metals in the root system (phytostabilization). Among these different processes, phytostabilization is of particular interest to be a low-cost and effective strategy. Moreover, this process is a characteristic of a wide range of plants which include also commercial species and model organisms such as Arabidopsis thaliana. On the other hand, some plants developed a rare adaptation to extract heavy metals from the soil and hyperaccumulate them into the shoot, such as Arabidopsis halleri. Thus, to gain insight into these two different strategies for managing heavy metals in a phystabilizing and hyperaccumulating Arabidopsis species, it is mandatory to comprehend protein-protein interactions (PPIs) as they play a crucial role underlying a specific response. To accomplish this aim, we conducted a weighted gene co-expression network analysis (WGCNA) from RNA-seq data of A. halleri root and shoot to identify and describe protein-protein interactions, for the first time, and to group genes with respect to their similar expression patterns. Moreover, taking advantage of protein-protein interactions already available for A. thaliana, we performed a comparison among specific organs of two species and highlighted pathways and functions, critical for phytostabilization and/or hyperaccumulation. This study will provide a clear preview of biological processes responsible for the different metal tolerance strategies and the biological processes peculiar to different organs of A. thaliana and helleri.