As one of the newest generations of nanoplatforms, smart nanotheranostics have attracted signifivant attentions for medical applications, especially in oncology and cancer treatment. Indeed, their capability to provide treatment and diagnosis simultaneously leads to reduce time and side effects along with improving the performance. This study aims to introduce a novel smart nano-platform composed of doxorubicin-loaded pH-responsive stealth niosomes containing CdSe/ZnS Quantum dots as an imaging agent. Drug loaded nano-platform was fabricated via thin-film hydration method and then evaluated using different physicochemical tests. The entrapment efficiency and release profile of doxorubicin were assessed at three different pH (4, 6.5, and 7.4). Biological features and imaging ability of the nanoparticles were also evaluated by MTT assay, apoptosis assay, and fluorescence microscopy. Results showed that the fabricated nanoparticles were round-shaped, with a mean size of about 100 ± 10 nm, -2 mV surface charge, and about 87% entrapment efficiency. The drug release profile presented a pH-responsive behavior (80, 60, and 40% drug release in pH 4, 6.5, and 7.4, respectively). The bio-activity assessments showed nearly 55% cytotoxicity effects via inducing cell apoptosis. Besides, the uptake of samples by the cells was confirmed through fluorescence imaging. Based on the results, this new nanoformulation could be considered as a candidate for future cancer theranostic applications.