Marine coastal areas are highly dynamic and fragile environments characterised by a complex interplay of biological, physical, and chemical factors. These areas are also affected by anthropogenic activities with the discharge of organic and inorganic contaminants that alters the quality of the environment. In this work, the effects of anthropogenic activities (i.e., urban and industrial development) on benthic foraminifera have been investigated along the A2TM core collected from the Sant’Elia-Foxi Canyon (Gulf of Cagliari, Sardinia—western Tyrrhenian Sea). The Gulf of Cagliari has experienced intense urbanisation since the beginning of the twentieth century with the establishment of petrochemical complexes and harbour activities. The A2TM core, dating from 1907 to 2013, was analysed with an integrated approach that includes grain size, organic matter, and benthic foraminifera characterisation compared with geochemical characterisation. The variations in the composition of the benthic foraminiferal assemblages and the Margalef diversity index are related to the altered environmental conditions that reflect the historical development of the area and to the land-based activities surrounding the Gulf of Cagliari. The statistical analysis identifies two main intervals (i.e., the years 1907–1986 and 1986–2013) that are typified by different benthic foraminiferal assemblages and diversity values. Accordingly, the increases in organic matter content and both organic and inorganic contaminants are well mirrored by a major drop in foraminiferal diversity after 1973 and a major foraminiferal turnover after 1989. The composition of the benthic foraminiferal assemblages in the uppermost part of the core (i.e., 1989–2013) might suggest a lowering of the oxygen availability at the seafloor. These changes might be related to the increase in organic matter and the silty fraction in the same interval likely triggered by damming on land and wetland reclamation.