Microplastics (MPs), antibiotics and heavy metals unavoidably contaminate the aquaculture environment, with serious ecological and human health consequences. Antibiotic-resistance genes (ARGs) and metal resistance genes (MRGs) are induced in microorganisms in the environment as a defence mechanism against antibiotics and heavy metals respectively. Furthermore, heavy metals in the aquaculture environment will cause bacteria to employ antibiotic resistance through co-selection (co-resistance or cross-resistance) and other potential mechanisms. MPs may also act as potential carriers of multidrug resistance in aquaculture environments because they are hotspots for the enrichment and transmission of antibiotic resistance. Multidrug-resistant (MDR) microorganisms in the aquaculture environment may infiltrate aquatic organisms via the food chain (eg MDR-microorganisms→myctophids→ tuna/ squid/ whales/ seabirds/ seals), and after long-term enrichment, they may gain access to the human body, posing a major risk to aquaculture and human health. As a result, this review article summarises contamination of MPs, heavy metal and antibiotics in global aquaculture settings; discusses the generation of ARGs, MRGs and common selection mechanisms for resistance development and emphasises the role of MPs as hot spots for antibiotic-resistance selective enrichment, as well as potential carriers of multi-drug-resistant genes (MDRGs), in the aquaculture environment, posing an increasing threat to aquaculture and even human health.