Rising global seafood consumption—reaching ~20  kg per capita in 2019—has heightened concerns over toxic heavy metals like mercury (Hg), cadmium (Cd), lead (Pb), and arsenic (As), which can exceed safety limits in predatory fish (e.g., Hg >1 mg/kg). This review quantifies the effectiveness of traditional and novel post-mortem processing methods to mitigate heavy metal risks in seafood. Acidic vinegar-based marinades reduced arsenic levels by ~90% (tenfold decrease) inrainbow trout, while boiling common carp fillets for 5 minutes decreased copper content by 54% and pan-frying achieved an 80% copper content reduction. Chelation techniques using food-grade agents such as sodium acetate removed up to 88.6% of Pb and 79.7% of Ni from green mussels, outperforming other citrate-based treatments. Combined treatments, like cysteine with EDTA, achieved up to 91% Hg reduction in mackerel. Advanced green technologies also demonstrated high efficiencies: supercritical CO₂ extraction reduced Pb, Cd, As, and Hg in fish oil by 93–98%, and electrocoagulation cut total heavy metals by ~90% in tilapia fillets. Optimized processing parameters, including treatment times (3–5 h), temperatures (30–50°C), and chelator concentrations (0.4–0.6 kg/m³), were critical for maximizing removal while maintaining seafood quality. These findings support integrating optimized post-mortem detoxification strategies into seafood processing to enhance safety, preserve nutrition, and promote sustainable seafood consumption.