Heavy metal contamination has been widely studied in coastal areas around the world. However, integrative studies of heavy metals pollution by monitoring and characterizing sediments, organisms, and biomarkers as well as their holistic interactions are rare. Here, we selected a developed coastal area in eastern Guangdong, China as the study field. Heavy metal analysis (both in sediment and mussel) and biomarker tests, including neutral red retention time test (NRRT) and micronuclei (MN) test, were employed in the current research. Anthropogenic activities influenced the heavy metal levels in sediments. Significant relationships (p < 0.05) were observed in the concentrations of Cd, Cu, and Zn between sediments and transplanted mussel, and significant relationships (p < 0.05) were also observed in between the concentrations of Cd, Cu, and Zn in sediments and the NRRT of mussel. The potential ecological risk index (RI) of sediments significantly correlated with NRRT (R = −0.991, p < 0.05). In Hao River, where the highest RI of sediments was found, the highest MN frequency and the lowest NRRT in mussels were detected simultaneously. The results indicated that the heavy metal pollution might cause subcellular toxic and genotoxic effects on mussels, especially for those from polluted areas (i.e., Hao River). The present study suggests that the transplanted green-lipped mussels are suitable for assessing heavy metal pollution, especially for Cd, Cu, and Zn.