Although various therapies have been developed for cancer treatment, chemotherapy plays a vital role, but still faces many challenges, such as severe cytotoxicity, side effects, multidrug resistance, and poor tumor selectivity. The development of targeted drug delivery has provided new strategies for addressing the limitations of the conventional chemotherapy, and has become more significant in clinical research in recent times. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumors. It is well-known that the extracellular pH of most tumor tissues is more acidic (pH 6.5–6.8) than that of normal tissues (pH 7.4). In our present review, we focus on some of the recent literature reports on the fabrication and application of pH-sensitive smart nanoparticles for tumor targeted drug delivery system. The strategies to the chemical design of these nanocarriers and their clinical findings are discussed. Particular focus is given to silica, chitosan, and silica–chitosan based nanocarriers. These smart nanoparticles will have a promising platform in improving human health and quality of life.