Purpose <p>Quality of life (QoL) in hemodialysis patients is influenced by clinical factors, but social-contextual determinants, including healthcare accessibility, caregiver support, and digital access, remain understudied. This study examined whether these modifiable social-contextual factors are independently associated with QoL beyond traditional clinical parameters.</p> Methods <p>A cross-sectional study of 309 patients receiving maintenance hemodialysis across three centers assessed QoL using the Kidney Disease Quality of Life Short Form-36 (KDQOL-36). Univariable analysis and multivariable linear regression were applied to identify factors independently associated with QoL.</p> Results <p>Travel time ≥ 45&#xa0;min was independently associated with worse disease burden (β = −9.37, <i>p</i> &lt; 0.001), symptoms (β = −8.93, <i>p</i> = 0.001), and physical health (β = −4.06, <i>p</i> &lt; 0.001); effect sizes numerically comparable to or exceeding those of diabetes within the same adjusted model. Patients managing self-care without family support showed significantly worse physical health versus those with spousal caregivers (β = −6.30, <i>p</i> &lt; 0.001). Lack of smartphone ownership predicted lower physical health scores (β = −2.96, <i>p</i> = 0.002). Hemoglobin remained the strongest clinical predictor across all domains; lower educational attainment and female sex were associated with higher disease burden.</p> Conclusions <p>Quality of life in hemodialysis patients is associated with modifiable social-contextual factors, including travel burden, caregiver support structures, and digital access, alongside anemia and educational attainment. Findings support the need for healthcare accessibility improvements, caregiver-inclusive care models, and attention to digital health equity in nephrology care.</p>