Occupational exposure to smoke and polycyclic aromatic hydrocarbons (PAHs) poses significant health risks, especially for commercial fish smokers who are regularly exposed to high levels of smoke and particulate matter. This study aimed to evaluate the exposure levels and assess the health risks associated with PAHs, phenols, phthalates, and substituted benzenes among 155 fish smokers in Ghana. A total of 155 urine samples from fish smokers across selected coastal regions in Ghana were collected and analyzed. The sample preparation was conducted using the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERs) method, as standardized by the Association of Official Analytical Chemists (A.O.A.C.). Analysis was performed utilizing the Shimadzu GC-MS QP 2020. The type of firewood used by fish smokers significantly influenced the levels of PAHs detected in the urine samples. Hardwoods such as odum, acacia, and cocoa, with their dense structures and combustion characteristics, were found to produce higher levels of PAHs. In contrast, softer woods like sugar cane and palm kernel released lower PAH levels during combustion. The findings indicate that fish smokers utilizing various wood types and unfiltered ovens, specifically the “Chorkor Oven,” are exposed to elevated levels of PAHs, phenols, phthalates, and substituted benzenes through inhalation during work hours. Cancer risk assessments revealed risk levels for PAHs ranging from 6.00E−04 to 4.14E−01, phenols from 0.00E+00 to 3.70E−01, substituted benzenes from 9.04E−08 to 1.99E−01, and phthalates from 3E−04 to 2.09E+04. These values exceed the limits by the U.S. Environmental Protection Agency (U.S.E.P.A.) of 10E−06. Furthermore, the estimated non-cancer hazard quotient values for hydrocarbons ranged from 8.42E+00 to 1.99E+01, all exceeding the threshold of 1, as outlined by both the U.S.E.P.A. and the World Health Organization (WHO), indicating substantial potential health risks for commercial fish smokers.