Malignant melanoma is the deadliest form of skin cancer with a stage 4 having a 5-year survival rate less than 10%. Current treatment strategies for malignant melanoma lacks the targeting capability and therefore leads to either decreased therapeutic efficacy or enhanced occurrence of adverse drug reactions. Psoralen and Quercetin are two molecules that have been found to possess profound anti-cancer activity. Nano drug delivery systems have been found to enhance the therapeutic efficacy while minimizing the adverse drug reactions. In the present study, nano formulations of psoralen and quercetin were prepared by solvent injection technique, following which the stability of the formulation was assessed by characterisation of the same through various sophisticated instruments such as Transmission Electron Microscopy and Scanning Electron Microscopy. Anticancer activity of the nano formulations was checked and compared by studying its effects on malignant melanoma cells both in vitro and in vivo. It was revealed that nano formulations of the individual drugs exhibited enhanced efficacy over unbound or free drugs while being out performed by the nano formulation composed of the combination of the two drugs, which itself was again found to be overshadowed by the group exposed to photodynamic therapy (PDT) before administration of the dual drug loaded nano formulation.