Antimicrobial resistance (AMR) presents a significant health problem globally with the majority of the burden coming from lower-middle-income countries. AMR surveillance under a One Health paradigm is critical for determining the relationships between clinical, animal, and environmental AMR levels. Allowing for a thorough knowledge of the interconnected variables contributing to resistance, which enables the development of effective solutions.This systematic review was conducted to determine the impact of antibiotics on the gene expression ofPseudomonas spp.In the East African Community. A comprehensive literature search was conducted across Web of Science, Scopus, and PubMed databases yielding 284 articles with 11 meeting the inclusion criteria after screening.We included the 11 studies from 5 East African Countries that are part of the East African Community, the results revealed a high prevalence of antimicrobial resistance inPseudomonas aeruginosa, with resistance rates above 90% for most tested antibiotics, exception of Amikacin, which remained effective due to its limited use. Common resistance genes reported included carbapenem-resistant genes likeblaNDM-1andblaVIM, the most common method used was disc diffusion method at (50%). The review also found high-risk clones, such as ST 244 and ST 357, that were associated with multidrug-resistant strains. Environmental isolates showed lower resistance rates (54%) than clinical pathogens (73%), indicating different selecting pressures. Majority of the studies were conducted in Kenya (30%) and Uganda (30%), indicating differences in research capabilities and healthcare facilities.These findings highlight the critical need for more surveillance, effective antimicrobial stewardship programs, and additional research to prevent antibiotic resistance and guide public health initiatives in the region.KEY FINDINGS OF THE STUDYPseudomonas aeruginosaisolates demonstrated substantial resistance to antibiotics, including cefepime, meropenem, levofloxacin, and ticarcillin-clavulanic acid as reported across various studies conducted in East Africa.Amikacin was reported to be more effective in more than 90% of the studies reported across East Africa as a potential treatment choice for multidrug-resistantPseudomonasinfections in the region.Carbapenem-resistant genes such asblaNDM-1, blaVIM, andblaOXA-48were found in a large number of clinical and environmental isolates.High-risk clones, such as ST 244 and ST 357 were reported to demonstrate clonal spread of multidrug-resistantPseudomonas aeruginosaacross East African healthcare settings.The disc diffusion method was the most popular antimicrobial susceptibility testing method (50%), owing to its low cost and simplicity.DNA extraction and PCR were used in 30% of the studies whereas more advanced approaches such as whole genome sequencing were less popular due to resource constraints.The majority of studies were undertaken in Kenya (30%) and Uganda (30%), with fewer studies in Tanzania and the Democratic Republic of the Congo (20%), demonstrating regional variations in research capacity and healthcare resources.