Oyster mushrooms (Pleurotus ostreatus var. Florida) degraded toxic polycyclic aromatic hydrocarbons (PAHs) more effectively when paired with certain natural metabolites. Indole-3-acetic acid and salicylic acid boosted breakdown by 25–70%, even making stubborn four-ring compounds like pyrene more accessible. Veratryl alcohol also improved degradation, while some flavonoids and organic acids hindered it. The process was linked to increased activity of laccase and versatile peroxidase—enzymes key to mycoremediation—showing how plant, bacterial, and fungal compounds can team up to speed pollutant cleanup.