Tuberculosis (TB) control remains severely challenged in Pakistan, with urban slum populations bearing a disproportionate burden due to pronounced socioeconomic disparities. The emergence of multidrug-resistant TB (MDR-TB) poses a critical public health threat; however, community-level data from these high-transmission settings remain limited, obscuring the true scale of the epidemic. A crosssectional study involving 3,317 individuals was conducted across the urban slum of six districts in Punjab, Pakistan between June 2024 and May 2025. Sputum samples were analyzed using smear microscopy, GeneXpert MTB/RIF, and comprehensive drug susceptibility testing (DST). Sociodemographic and clinical data were collected to assess potential risk factors. The prevalence of Mycobacterium tuberculosis (MTB) infection confirmed by GeneXpert was 17.0% (564/3,317), significantly higher than the 12.8% detected by smear microscopy. Initial molecular testing identified rifampicin resistance in 40.2% (227/564) of MTB-positive cases, with 39.0% (220/564) fulfilling the criteria for MDR-TB. The MDR-TB burden was markedly higher among retreatment cases (68.1%) compared with new cases (29.8%) and exhibited significant geographic clustering, with prevalence exceeding 53% in Lahore and Kasur. Smoking emerged as the most significant risk factor, observed in 73.8% of MTB-positive individuals (P < 0.001). Among rifampicin-resistant isolates subjected to extended DST, resistance rates were 96.9% for isoniazid, 100% for rifampicin, 46.3% for ofloxacin, 4.4% for amikacin, 22.9% for kanamycin, and 8.4% for capreomycin. The prevalence of MDR-TB in the urban slums of Punjab was alarmingly higher than national and global estimates. These findings necessitate an urgent need for expanded molecular diagnostics, active case-finding, and targeted public health interventions in these marginalized communities. Without immediate and coordinated action, urban slums risk becoming focal points for the accelerated emergence of untreatable TB.  Kulcsszavak: tuberculosis, multidrug-resistant TB (MDR-TB), urban slums, drug susceptibility, GeneXpert MTB/RIF, public health, pulmonary TB, antimicrobial resistance