Toxicology-related deaths are understudied, especially in regional and local settings. Post-mortem toxicological data may help identify regional drug use patterns and guide targeted local interventions. A five-year retrospective study was carried out on all toxicology-related deaths admitted to Gold Coast University Hospital, Queensland, Australia. A total of 291 toxicology-related deaths were identified in which the majority were drug related (n = 254, 87.3%). Drug-related deaths were more commonly associated with polydrug use (median = 3.4 drugs). Prescribed drugs were most frequently detected and were more commonly associated with the older population (p < 0.05). Illicit drugs were mostly detected in the younger population, in particular males (p < 0.05); paracetamol and/or antidepressants were more commonly detected in females (p < 0.05). Alcohol was rarely a sole cause of non-drug-related toxicology-related deaths, while the most common cause of gas/fume-related death was carbon monoxide. Public health interventions and better regulation of access to various drug and non-drug substances, and a review of potential inappropriate prescribing practices may help address the burden of toxicology-related deaths. In addition, more studies to understand the differences in toxicology-related death in relation to sex and age could help identify modifiable risk factors.