The Manila clam Ruditapes philippinarum is an invasive bivalve in Europe, widely distributed, with a great ability to tolerate a broad range of environmental conditions. Despite the ability to reflect contamination, its suitability as bioindicator is not consensual. This study provided clarification on this issue by evaluating the ability of R. philippinarum to signalise trace element contamination in an estuary chronically impacted by metals and metalloids (Tagus estuary, Portugal). A multidimensional approach was carried out in two differently contaminated sites (Barreiro – BAR; Alcochete – ALC) in warm and cold periods, combining sediment contamination, bioaccumulation of trace elements (As, Cd, Pb and Hg), and a battery of oxidative stress biomarkers in two R. philippinarum organs (digestive gland and gills). Sediments from BAR exhibited higher concentrations of all the elements than those from ALC, in line with the anthropogenic pressures identified for both estuarine areas. Likewise, clams from BAR showed higher concentrations of As and Pb in the digestive gland (cold period) and Pb in the gills (warm and cold periods) in comparison with ALC. These results suggest the capacity of R. philippinarum to reflect external levels of exposure to those elements into tissue loads. However, an opposite spatial variation was consistently found for Hg accumulation in the digestive gland and gills in both periods, as well as for Cd in the gills in the warm season. The results reinforce the idea that trace element accumulation patterns depend not only on the external bioavailability, but also on the toxicokinetics that is trace element-specific. Despite the two contrasting patterns found for bioaccumulation in R. philippinarum (mainly Pb vs. Hg), oxidative stress parameters were able to signalise BAR as the most impacted area. In fact, the digestive gland of BAR clams exhibited higher GST activity and GSHt levels (in both sampling periods) and SOD activity (warm season), presumably to cope with the enhanced accumulation of Pb and As. Moreover, variations of gills’ CAT and SOD activities (warm period) agreed with the elevated accumulation of Pb at BAR. Overall, the characteristics of this invasive species could lead to a biased interpretation of the environmental quality status, particularly when based on trace element bioaccumulation only, reinforcing the need to adopt a multi-level/-species approach on environmental assessment studies.