Major depressive disorder (MDD) is the leading cause of disability worldwide, with approximately half of patients demonstrating resistance to standard treatments. Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved intervention that targets the left dorsolateral prefrontal cortex (DLPFC), a region implicated in MDD and consistently shown to be hypoactive in affected individuals. Recent evidence underscores the clinical superiority of functional MRI (fMRI)-guided rTMS targeting the subgenual anterior cingulate cortex (sgACC), a region functionally connected to the DLPFC, over conventional scalp-based approaches. While most studies have focused on anticorrelated functional connectivity (FC) targets, this study investigates whether positively correlated sgACC targets may yield enhanced engagement of the sgACC, which leads to superior reduction in depressive symptoms. We hypothesized that (1) fMRI-guided TMS would produce a significant negative change in sgACC blood-oxygen-level-dependent (BOLD) signal, reflecting effective regional engagement, and (2) stimulation of positively correlated sgACC targets would yield greater TMS-evoked responses relative to negatively correlated targets. Participants (ages 18–65) met DSM-5 criteria for MDD (≥90%) or persistent depressive disorder (≤10%), with baseline PHQ-9 scores ≥10. Individualized positive and negative sgACC FC targets were derived from baseline fMRI scans. Participants were then randomized to receive rTMS to either positively or negatively correlated sgACC targets, administered five days per week for six weeks (30 sessions total). Each session consisted of two sets of intermittent theta-burst stimulation (iTBS), delivering 2,400 pulses in total. Combined TMS/fMRI sessions were conducted at pre-treatment, mid-treatment, and post-treatment stages to quantify sgACC BOLD responses under TMS-on versus TMS-off conditions. Clinical outcomes were measured with the Montgomery–Åsberg Depression Rating Scale (MADRS), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7). Preliminary analyses indicate robust clinical improvements across all measures. MADRS (n=18), PHQ-9 (n=19), and GAD-7 (n=19) scores showed statistically significant reductions following treatment (all p < 0.001, Wilcoxon signed-rank tests). This reflects meaningful decreases in depressive and anxiety symptom severity. These findings support the hypothesis that fMRI-guided rTMS effectively engages the sgACC. Although data collection is ongoing and the current sample size limits statistical power, these early results suggest that individualized, connectivity-based targeting improves the precision and efficacy of rTMS beyond scalp-based approaches. This study adds to a growing body of evidence supporting connectivity-informed neuromodulation as a strategy to selectively engage subcortical regions critical to depression, which may inform future treatments for patients with treatment-resistant MDD.