Nanotechnology-based combination anticancer therapy offers novel approaches to overcome the limitations of single-agent administration. The emerging siRNA technology combined with chemotherapy has shown considerable promise in anticancer therapy. There are three main challenges in the fabrication of siRNA/chemotherapeutic drug co-loaded nanovectors: adequate cargo protection, precise targeted delivery, and site-specific cargo release. This review presents a summary of the nanosystems that have recently been developed for co-delivering siRNA and chemotherapeutic drugs. Their combined therapeutic effects are also discussed.