The present study provides an overview of the challenges and opportunities in processing complex gold-copper ores. The systematic literature review was conducted using Scopus database and seven-step methodological approach. The study indicates that the major challenges in processing complex gold-copper ores through the conventional cyanidation method include (1) increase in cyanide consumption; (2) increase in cyanide destruction cost; (3) low gold recovery; (4) decrease in adsorption efficiency; (5) decrease in electrowinning efficiency, and (6) difficulties in the measurement of free cyanide concentration in the leaching system. Moreover, the study indicates that several methods have been developed and some have been implemented in the mining industry for processing complex gold-copper ores. This includes ore segregation, pre-aeration, pre-treatment methods (e.g., ammonia), alternative lixiviants (e.g., thiosulfate, thiocyanate, glycine), cyanide destruction methods, and cyanide and copper recovery technologies. The study concluded that using lixiviant mixtures (e.g., cyanide-glycine), pre-treatment with environmentally friendly reagents (e.g., glycine) and the integrated membrane-based process (SuCy process) are new directions in processing complex gold-copper ores. However, more investigations are required to advance these processes to a commercial scale.