This retrospective cohort study identified factors associated with loss of follow-up and death due to tuberculosis (TB) in the homeless population (HP) in Brazil, estimating odds ratios (OR) and their 95% confidence intervals (95%CI) by multinomial logistic regression. A total of 3,831 TB cases in this population were analyzed, of which 57.0% had unfavorable outcomes. Loss of follow-up was associated with: history of abandonment (OR=2.38; 95%CI 2.05-2.77), unknown HIV serology (OR=1.79; 95%CI 1.38-2.32), HIV coinfection (OR=1.73; 95%CI 1.46-2.06), drug use (OR=1.54; 95%CI 1.31-1.80), age (OR=0.98; 95%CI 0.97-0.99), mixed clinical form (OR=0.64; 95%CI 0.42-0.97), extrapulmonary form (OR=0.46; 95%CI 0.29-0.73), government beneficiary (OR=0.64; 95%CI 0.50-0.81), and supervised treatment (OR=0.52; 95%CI 0.45-0.60). Regarding death, the following were associated: age (OR=1.03; 95%CI 1.01-1.05), unknown HIV serology (OR=2.39; 95%CI 1.48-3.86), alcohol consumption (OR=1.81; 95%CI 1.27-2.58), and supervised treatment (OR=0.70; 95%CI 0.51-0.96). Overlapping vulnerabilities in the health-disease process of homeless individuals with TB were observed, requiring comprehensive and cross-sectoral care practices.