Background: Modic changes (MCs) are vertebral endplate signal alterations frequently observed in degenerative lumbar spine disease. Their impact on the efficacy of non-surgical interventions such as epidural steroid injections (ESI) and facet joint blocks (FJB) remains uncertain. This study aimed to evaluate the influence of MCs on pain and functional outcomes after ESI and FJB in patients with chronic low back pain (LBP). Patients and Methods: In this prospective randomized study, 48 patients with chronic LBP (>6 months) were recruited at Zagazig University Hospitals between January and December 2024. Patients were divided into two groups: with MCs (n = 24) and without MCs (n = 24). Each group was further subdivided into ESI and FJB subgroups (n = 12 each). Pain and disability were assessed using the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) at baseline, 6 weeks, and 12 weeks. Results: Baseline demographics and clinical characteristics were comparable between groups. At 12 weeks, Modic-positive patients treated with ESI demonstrated significantly higher pain scores (VAS 7.33 ± 0.82) compared with Modic FJB (6.33 ± 1.03) and both non-Modic subgroups (5.83 ± 0.75 and 5.83 ± 0.98, p = 0.029). ODI outcomes mirrored this trend, with 50% of Modic ESI patients classified as crippling versus none in the other groups (p < 0.001). Non-Modic FJB patients achieved the greatest pain reduction (median VAS change −14.06%, p = 0.011), while Modic ESI patients experienced worsening pain (+14.29%). Conclusion: MCs, particularly in patients receiving ESI, are associated with poorer pain relief and functional recovery following injection therapy. FJB appears relatively more effective in Modic-positive patients. Tailored strategies considering Modic status are warranted to optimize outcomes in chronic LBP. Keywords: Modic changes; chronic low back pain; epidural steroid injection; facet joint block.