Background: Chimeric antigen receptor (CAR)-T cell therapy has shown remarkable success in the treatment of hematological cancers. Remission rates of up to 80% are achieved, yet 40-60% of patients do not respond long-term. Low CAR-T cell exposure has been associated with treatment failure, suggesting that higher doses might achieve improved responses. However, as there is no clear dose-exposure relationship for CAR-T cell therapy, alternative methods than dose titration to increase exposure are needed. This work aimed to identify both actionable variables which could be modified towards a favorable CAR-T cell kinetic profile, and suitable in silico models for use in the development of such optimization strategies. Methods: A literature review was performed to identify actionable variables regarding CAR-T cell expansion and persistence during CAR-T cell development, manufacturing, or clinical treatment. In addition, currently available in silico models and their potential application to guide treatment optimization were analyzed. Results: The identified actionable variables include i) development: selection of costimulatory and hinge domains, CAR affinity; ii) manufacturing: time of apheresis with respect to last chemotherapy, apheresate treatment, expansion duration, cytokines in the expansion medium and their concentration; iii) clinical treatment: tumor debulking and lymphodepleting regimen. Published mechanistic and empirical cell kinetic/dynamic models to aid in developing optimization strategies for these variables and learn from emerging data were identified. Conclusion: In absence of a clear dose-exposure relationship, several actionable variables can be modified to increase CAR-T cell exposure. Fit-for-purpose in silico models are available to guide the development of such optimization strategies.