Bacterial therapeutics present a way to address drug delivery challenges in solid tumor environments (TMEs) by exploiting native adaptations of microbes to overcome TME inhibition. Recent investigation of the tumor microbiome has allowed for the development of novel delivery mechanisms optimized through chassis natively found in the TME. The further evaluation and optimization of these bacterial "vehicles" and their synthetic genetic circuitry are the main focus of the Biodynamics lab at UCSD. Evaluation of engineered microbes against discrete TME niches such as hypoxia, fibrosis, immunosuppression, and metabolomic shifts yields crucial information on shortcomings in current circuitry, and allows for iterative re-engineering to overcome TME inhibition, increase drug delivery efficiency, and maximize therapeutic efficacy. These evaluations are carried out via microfluidic dissection of TME niches, high-throughput organoid co-culture platforms, and ultimately in vivo validation. Using this design-build-test-learn (DBTL) pipeline, we aim to rationally design effective synthetic microbial therapeutics tailored to specific tumor-type niches, and alleviate canonical drug delivery challenges associated with TME inhibition.