A range of oxobis(phenyl‐1,3‐butanedione) vanadium(IV) complexes have been successfully synthesized from cheap starting materials and a simple and solvent‐free one‐pot dry‐melt reaction. This direct, straightforward, fast and alternative approach to inorganic synthesis has the potential for a wide range of applications. Analytical studies confirm their successful synthesis, purity and solid‐state coordination, and we report the use of such complexes as potential drug candidates for the treatment of cancer. After a 24 hour incubation of A549 lung carcinoma cells with the compounds, they reveal cytotoxicity values elevenfold greater than cisplatin and remain non‐toxic towards normal cell types. Additionally, the complexes are stable over a range of physiological pH values and show the potential for interactions with bovine serum albumin.