The phospholipids complexation technique is the best solubility enhancement technology, and as a result, many authors have successfully used it to increase the solubility, permeability, and oral bioavailability of numerous drug molecules. The drug belongs to BCS calss II which having poor solubility and higher permeability could have been limited clinical use. Hence the strategy to alter the biopharmaceutical properties should be employed. In this study the Mlx-phospholipid (Mlx-PL) complex was prepared for enhancement of solubility and efficacy of meloxicam which is an NSAID having proven anticancer activity. The Mlx-PL complex was synthesized by solvent evaporation method and quality attributes were optimized by QbD based Box-Behnekn design of experiment. The optimized formulation was evaluated for physicochemical properties and functional patrameters like entrapment efficiency and drug release study. The cytotoxicity study was also carried out in humane adenocarcinoma breast (MCF-7) cell line. The prepared complex was demonstrated form dynamic light scattering which shows particle size distribution of about 122.4 nm and zeta potential about −35.8 mV. The thermal analysis and FTIR study revealed the compatibility of drug with the excipients. It also showed the successful formation of Mlx-PL complex with improved solubility when evaluated for apparent solubility in various organic solvents and in water. The Mlx-PL complex entrapped about 91.77% drug encapsulation and releases the 94.85±3.0% drug after the end of 72 h when demonstrated for in vitro drug release study. The in vitro cytotoxicity study showed enhanced efficacy of Mlx-PL complex than the pure Mlx suspension. Hence the overall results of this study proved the excellent potential of phospholipid complex for solubility enhancement and improved efficacy of the anticancer drugs which belongs to BCS class II.