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Simple Summary: Despite its high organic matter content, sewage sludge contains significant quantities of heavy metals, including those designated as hazardous, such as cadmium, nickel, chromium, mercury, copper, lead, and zinc, which, as a consequence, have a negative impact on living organisms. The current research sought to study the effect of dumping sludge, as one of the sources of pollution with heavy metals, on biodiversity and to assess the bioremediation and stress defense strategies of a tolerant plant species. The obtained results showed that soil pollution by heavy metals has a substantial influence on plant diversity. The selected species, Amaranthus retroflexus L., showed a high biological concentration factor (BCF) and low translocation factor (TF) for Cu, As and Ni. The stress defense strategies of A. retroflexus grown under complex heavy metals contamination are studied and discussed. Accumulation of heavy metals in soil is becoming an increasingly serious eco-environmental problem. Thus, investigating how plants mitigate heavy metal toxicity is necessary to reduce the associated risks. Here, we aimed to assess the bioremediation and stress defense strategies of tolerant plant species grown under complex heavy metals contamination. To this end, a field study was conducted on the vegetation cover of sites with different soil pollution levels. Forty-two plant species that belong to 38 genera and 21 families were identified. The pollution had a significant impact on plant richness in the polluted sites. Out of several screened plants, Amaranthus retroflexus L. was selected because of its high relative density (16.7) and a high frequency (100%) in the most polluted sites. The selected species showed a high biological concentration factor (BCF) and low translocation factor (TF) for Cu, As and Ni. To control the heavy metal-induced oxidative damage, A. retroflexus invested in detoxification (metallothionein and phytochelatins, glutathione and glutathione-S-transferase (GST). At the organ level, oxidase damage (H2O2, lipid and protein peroxidation) was observed, particularly in the roots. To mitigate heavy metal oxidative stress, antioxidant mechanisms (e.g., tocopherols, glutathione, peroxidases, catalase, peroxide dismutase and ASC-GSH cycle) were upregulated, mainly in the roots. Overall, our results suggested the potentiality of A. retroflexus as a promising bioremediatory and stress-tolerant plant at the same time; moreover, defense and detoxification mechanisms were uncovered. [ABSTRACT FROM AUTHOR]