The Colombian Caribbean faces environmental challenges due to urbanization, industrialization, and maritime activities, which introduce pollutants such as heavy metals, hydrocarbons, and microplastics into aquatic ecosystems. Perna viridis (Asian green mussel), an invasive species that has been established in Cartagena Bay since 2009, exhibits potential bioaccumulation capacity, making it a promising biomonitor. This study assessed the concentrations of mercury (Hg), cadmium (Cd), lead (Pb), and selenium (Se) in P. viridis across two key sites—a port area at the Cartagena Bay (CB) and Virgen marsh (VM) in Colombia—from 2020 to 2023. Seasonal variations driven by La Niña and El Niño phenomena significantly influenced metal concentrations, with transitional periods modulating pollutant accumulation. The levels of trace metals in soft tissue of P. viridis (dry weight) ranged from 0.0003 to 0.0039 µg/g (Cd), 0.04 to 0.21 µg/g (Hg), 0.05 to 1.18 µg/g (Pb), and 0.0029 to 0.0103 µg/g (Se). In suspended particulate matter (SPM), Cd ranged from 0.07 to 0.33 µg/g; Pb ranged from 4.94 to 25.66 µg/g; and Hg ranged from 0.18 to 1.20 µg/g. Results revealed differences in metal concentrations between sites and seasons, highlighting the role of environmental and anthropogenic factors in pollutant distribution. The findings confirm P. viridis as an effective biomonitor of complex pollution scenarios in Cartagena Bay. However, its invasive status highlights ecological risks to be addressed, such as interaction with native bivalves and benthic community structures. These results emphasize the need for ongoing monitoring efforts to mitigate pollution and preserve marine biodiversity in the Colombian Caribbean.