Malaysia Klang River covering states of Selangor and Kuala Lumpur, has been severely polluted from urbanization, industrialization and increased hospitals. By serving as reservoir for bacterial gene transformation, Multidrug Resistant (MDR) strains especially Extended Spectrum Beta Lactamase (ESBL) resistant strains of Klebsiella pneumoniae (K. pneumoniae) have increased. To identify MDR K.pneumoniae; phenotypically determine ESBL resistant traits and molecular characterize these strains, 50 water samples were collected along Klang River and their physicochemical properties were determined. Gram-negative K. pneumoniae isolates were tested for multidrug and ESBL resistance using Kirby-Bauer method. DNA of ESBL resistant K. pneumoniae were extracted and amplified using Polymerase Chain Reaction (PCR); and conferred using blaTEM and blaCTX-M genes. Through β-lactamase gene sequencing and docking studies, the effectiveness of drugs against ESBL resistant K.pneumoniae were determined. A total of 31 (62.0%) K.pneumoniae were isolated with 12 (38.7%) positive MDR strains and 5 (41.7%) ESBL resistant strains. Only 1 (20%) blaTEM gene and 4 (80%) blaCTX-M genes were detected with Ceftriaxone (CRO) as the most effective drug showing highest binding energy (-9.2Kcal/mol) against ESBL resistant K. pneumoniae. With high prevalence of CTX-M-type ESBL resistant K.pneumoniae in Klang River, effective environmental and antibiotic controls should be adopted.