We describe a case series of fve infants (age range: 1–90 days; 4 females and 1 male) who presented to Al Jalila Chil dren’s intensive care units (ICU) with complex multisystem disorders. Patients were Emirati, Kenyan, Jordanian, Filipino, or Pakistani. Trio rapid whole genome sequencing (rWGS) was performed on all fve patients and their parents within the hospital’s genomics facility. Results were returned within ~37 h from blood sample draws and were diagnostic in 3 out of 5 patients. Positive fndings were a homozygous pathogenic variant in POMT1 gene causing muscular dystro phydystroglycanopathy, a mosaic tetrasomy of the short arm of chromosome 12 (12p13.33p11.1) causing PallisterKillian syndrome, and compound heterozygous pathogenic variants in the LIPA gene causing lysosomal acid lipase defciency and Wolman disease. The rWGS analysis provided fast and precise diagnostic fndings in those 3 patients and also aided in devising better management plans for them in the intensive care setting. For example, the 3-monthold infant with pathogenic variants in the LIPA gene is now a candidate for an FDA-approved, potentially lifesaving enzyme replacement therapy (sebelipase alfa). Our case series emphasize the feasibility and utility of rWGS in pedi atric intensive care setting, in a diverse population that has long been underserved in genomic services. Signifcant investments in local healthcare infrastructure are needed, globally, for more equitable access of genomic medicine among vulnerable patients.