Autologous stem cell transplantation (ASCT) is integral to treating newly diagnosed multiple myeloma (MM). While novel therapies improve response rates, they also hinder stem cell mobilization. This study evaluates the impacts of induction regimens on mobilization, collection, and ASCT outcomes. We analyzed 228 patients divided into three groups: bortezomib-thalidomide-dexamethasone (VTD, N = 117); bortezomib-lenalidomide-dexamethasone (VRD, N = 57); and daratumumab-VTD (DVTD, N = 54). Baseline characteristics showed no significant differences among the groups. Chemo-mobilization was most common in VTD (20.5%) compared to VRD (12.3%) and DVTD (5.6%). Total CD34 + cell yield (x10⁶/kg) was highest in VTD (7.1 ± 3.5) compared to VRD (5.8 ± 3.2) and DVTD (5.4 ± 2.4) [p = 0.0001]. Second mobilization was required most frequently in VRD (40.4%) compared to DVTD (24.1%) and VTD (16.2%) [p = 0.0010]. Plerixafor use was highest in VRD (40.4%) compared to DVTD (24.1%) and VTD (12.0%) [p = 0.0001]. Mobilization duration was longest in VRD (4.0 ± 1.9 days) and shortest in VTD (3.2 ± 1.7 days) [p = 0.0038]. Infused CD34 cells and platelet engraftment times were comparable among groups. Neutrophil engraftment was delayed in VRD (12.1 ± 0.9 days) compared to DVTD (11.8 ± 1.2) and VTD (11.6 ± 0.7) [p = 0.0014]. Prompt stem cell collection is essential in lenalidomide regimens to minimize mobilization challenges. While DVTD demonstrated comparable mobilization efficiency, it produced fewer CD34 cells than VTD, indicating potential challenges.