The dwindling availability of agricultural land, caused by factors such as rapid population growth, urban expansion, and soil contamination, has significantly increased the pressure on food production. To address this challenge, cultivating non-food crops on contaminated land has emerged as a promising solution. This approach not only frees up fertile soil for food production but also mitigates human exposure to contaminants. This work aimed to examine the impact of soil contamination with Cd, Pb, Ni, and Zn on the growth, productivity, metal accumulation, and the tolerance of five lignocellulosic non-food crops: switchgrass (Panicum virgatum L.), biomass sorghum (Sorghum bicolor L. Moench), giant reed (Arundo donax L.), African fodder cane (Saccharum spontaneum L. spp. aegyptiacum Willd. Hackel), and miscanthus (Miscanthus × giganteus Greef et Deu.). A two-year pot experiment was conducted in Greece, Italy, and Portugal, following the same protocols and applying various levels of metals: Cd (0, 4, 8 mg kg−1), Pb and Zn (0, 450, 900 mg kg−1), and Ni (0, 110, 220 mg kg−1). The experimental design was completely randomized, with three replicates for each treatment. The results showed that switchgrass and sorghum generally maintained their height and productivity under Cd and Pb stress but were adversely affected by high Zn and Ni concentrations. Giant reed and African fodder cane showed reduced height and productivity at higher Ni and Zn levels. Miscanthus exhibited resilience in height but experienced productivity reductions only at the highest Zn concentration. Heavy metal uptake varied among crops, with switchgrass and sorghum showing high Cd and Pb uptake, while giant reed accumulated the most Cd and Zn. Miscanthus had the highest Ni accumulation. The tolerance indices indicated that switchgrass and sorghum were more tolerant to Cd and Zn at lower concentrations, whereas miscanthus had lower tolerance to Cd but a higher tolerance to Zn at higher concentrations. Giant reed and African fodder cane demonstrated stable tolerance across most heavy metals. Accumulation indices highlighted the effectiveness of switchgrass and sorghum in Cd and Pb uptake, while miscanthus excelled in Ni and Zn accumulation. The cluster analysis revealed similar responses to heavy metal stress between African fodder cane and giant reed, as well as between sorghum and miscanthus, with switchgrass displaying distinct behavior. Overall, the study highlights the differential tolerance and accumulation capacities of these crops, indicating the potential for phytoremediation applications and biomass production in heavy metal-contaminated soils.