Identify the pathway by which social determinants of health (SDoH) variables impact systolic blood pressure (SBP) in immigrants. Latent variables were used to assess the relationship between SDoH and SBP. Latent variables were identified using confirmatory factor analysis (CFA) for (1) global socioeconomic status (SES) (education, income, number of hours worked per week), (2) stressors of immigration (life-course SES, immigration stress, immigration demand), (3) adaptation to immigration (perceived discrimination, perceived stress, health literacy), and (4) burden of disease (disability, comorbidities, chronic pain). Structural equation modeling (SEM) was used to investigate the relationship between immigrant specific latent variables and SBP. The study included 181 adult immigrants. The initial model (chi2 (77, n = 181) = 302.40, p < 0.001, RMSEA = 0.086, CFI = 0.84, TLI = 0.78, CD = 0.91) showed that stressors of immigration had a direct relationship with SBP (−0.35, p = 0.033); global (SES) had a direct relationship with burden of disease (−0.70, p = 0.007) and an indirect relationship with SBP by way of burden of disease (0.24, p = 0.015). The final model (chi2 (69, n = 181) = 149.98, p < 0.001, RMSEA = 0.054, CFI = 0.94, TLI = 0.91, CD = 0.96) maintained that global SES had a direct relationship with burden of disease (−0.40, p < 0.001) and an indirect relationship with SBP by way burden of disease (0.34, p < 0.001). This study suggests a direct relationship between burden of disease and SBP, and an indirect relationship between SES and SBP. Development of interventions should take burden of disease into account as a direct driver of blood pressure in immigrants, and address factors related to SES.