Intracellular microbes are actively present in various tumor types in low biomass and play major role in metastasis. Eliminating intracellular microbes on a cellular level with precision remains a challenge for addressing this, we designed a screening pipeline to characterize intracellular microbes and their interaction with host cells. For that we used host and microbial in-vitro model cell line as HeLa and microbial strain as Escherichia coli 25922. To study dynamics of intracellular microbes we used antibiotics (ampicillin, roxithromycin, ciprofloxacin) and chemotherapy drugs (doxorubicin and cisplatin) as external environmental stress conditions. To effectively eliminate intracellular microbes Permutation Orthogonal Arrays (POA) approach was applied to acquire optimal drug combination regimen in dose and sequence of drugs which reduced 90-95% of intracellular microbial load.