An integrated ecotoxicological study based on bioaccumulation and biomarker responses in sea urchin, mussel, and fish was conducted in Vlora Bay (Albania). Despite several past industrial activities and current increase of anthropogenic impact characterising Vlora Bay, no ecotoxicological data have been published so far, underlining the need to investigate the area and to validate the ecotoxicological approach. Heavy metals, polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OC), and polychlorinated biphenyls (PCBs) were measured in native sea urchin (Arbacia lixula), Mediterranean mussel (Mytilus galloprovincialis), and red mullet (Mullus barbatus). Several biomarkers such as expression of heat-shock proteins (HSP-70) in sea urchin (PCR), detoxification enzyme activities and apoptosis in mussels, and acetylcholinesterase (AChE) activity in mussels and red mullet were investigated. Overall, ecotoxicological data suggest an environmental quality of Vlora Bay resembling a marine protected area except for levels of Cd, Ni, and Hg in mussels and red mullet gonads; these results are in agreement with past industrial activities. OC pesticides were found to be below the detection limit in sea urchin. PCB levels were very low (4.13–13.87 ngg−1 fresh weight) both in mussels and fish, while PAHs were similar to those reported for moderately impacted areas. No exposure to neurotoxic pesticides (physiological AChE activities) or to cytotoxic contaminants (low apoptosis frequency: <1%) can be inferred both in mussels and fish. . Detoxification enzyme activities in mussels were highly similar compared with those reported for low-impact areas. The results of the present ecotoxicological study on Vlora Bay also support its suitability in environmental quality assessment of marine coastal areas.