Platinum drugs are common in chemotherapy, but their clinical applications have been limited due to drug resistance and severe toxic effects. The combination of platinum drugs with other drugs with different mechanisms of anticancer action, especially checkpoint inhibitors, is increasingly popular. This combination is the leading strategy to improve the therapeutic efficiency and minimize the side effects of platinum drugs. In this review, we focus on the mechanistic basis of the combinations of platinum-based drugs with other drugs to inspire the development of more promising platinum-based combination regimens in clinical trials as well as novel multitargeting platinum drugs overcoming drug resistance and toxicities resulting from current platinum drugs.