There is a continuous demand for sensitive and efficient cancer drug delivery systems that, when administered at low concentrations, are capable of detecting early-stage pathological conditions and increasing patient survival without adverse side effects. Recent developments in the design of chitosan-based smart drug delivery nanocomplexes are able to respond to the distinctive features of the tumor microenvironment and have provided powerful tools for cancer targeted treatment. Due to its biocompatibility and pH-responsiveness, chitosan has emerged as a promising candidate for the formulation of novel, supramolecular multifunctional materials. This review will first present an overview of the characteristics of solid tumors and their microenvironment, with a particular emphasis on the role of pH as a key factor. In the second part of the review, the stimuli-responsive potential of chitosan-based micelles, current challenges in delivery, and strategies to improve therapeutic efficacy will be discussed.