Nanostructured colloidal self-assembly (NCS) is one of the most promising drug delivery carriers in cancer treatment. The present research work aimed towards synthesizing meloxicam (MLX) loaded NCS for its improved circulation half-life and increased cellular internalization. NCS was formulated using glyceryl monoolein, Pluronic® F127, and MLX. Quality by Design experiments with a quadratic model was subjected to optimization of the formulation. The optimized NCS with an average particle size of 185.5 ± 3.02 nm showed higher MLX encapsulation (94.74 ± 3.41%) and sustained release behavior of MLX up to 24 hr. in vitro cytotoxicity of the developed NCS with MCF-7 and MDA-MB-231 cell lines confirmed lower cell viability and a higher rate of cell growth inhibition. This MLX loaded NCS showed dual activity as an antitumor and anti-inflammatory in highly invasive estrogen-dependent MDA-MB-231 cells due to the high expression of cyclooxygenase-2 (COX-2). Besides, an activity of the MLX-NCS was also observed in 3D printed MCF-7 cells. This investigation shows the possible use of MLX-NCS as an efficient cancer drug delivery system with excellent colloidal stability, sustained release of MLX, enhanced antitumor and anti-inflammatory efficacy in 3D printed scaffolds. In contrast to toxicity study in 2D culture, the 3D constructs revealed the activity of the MLX via COX-2 independent mechanism and demonstrated that the relationship between COX-2 expression and antitumor activity of inhibitors is limited. In conclusion, the overall observations and results of this study strengthen the hypothesized development of NCS as a next-generation therapeutics regimen for cancer therapy.