Current drug therapy against infections is threatening to become obsolete due to the poor physical, chemical, biological and pharmacokinetic properties of drugs, followed by high risk of acquiring resistance. Taking into account the significant benefits of nanotechnology, nano-based delivery of anti-infectious agents is emerging as a potential approach to combat several lethal infections. Co-delivery of multiple anti-infectious agents in a single nano-based system is beginning to show significant advantages over mono-therapy, such as synergism, enhanced anti-microbial activity, broad anti-microbial spectrum, reduced resistance development, and improved and cost-effective treatment. The current review provides a detailed update on the status of various lipid and polymer based nano-systems used to co-deliver multiple anti-infectious agents against bacterial, HIV and malarial infections. It also identifies current key challenges and suggests strategies to overcome them, thus guiding formulation scientists to further optimize nano-based co-drug delivery as an approach to fight infections effectively.