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Abstract Introduction: Bispecific antibodies and Chimeric Antigen Receptor (CAR)-T cell therapies are transformative treatments for Multiple Myeloma (MM) and Diffuse Large B-Cell Lymphoma (DLBCL). However, real-world data comparing the patient populations receiving these novel immunotherapies is limited. This study characterizes the distinct clinical profiles and treatment patterns of patients receiving bispecifics versus CAR-T therapy across these two malignancies. Methods: This retrospective analysis used real-world data from the Ipsos Global Oncology Monitor to analyze US patient-level data from June 2024 to May 2025. The analysis included 597 MM patients (126 on bispecifics; 471 on CAR-Ts) and 502 DLBCL patients (129 on bispecifics; 373 on CAR-Ts) submitted online by 188 physicians; recruited physicians were primary treaters screened for caseload. We compared patient demographics, comorbidities, ECOG performance status, disease characteristics, treatment settings, and prescriber satisfaction between the two therapeutic classes within each disease. Results: In both MM and DLBCL, reported patients treated with bispecifics were older than those receiving CAR-T therapy (mean age in MM: 67.6 vs 63.1 years; in DLBCL: 68.4 vs 62.0 years). Patients in the bispecific cohort consistently demonstrated poorer performance status (ECOG ≥2 in MM: 27% vs 18% (p<0.05); in DLBCL: 19% vs 9%) and had a higher prevalence of comorbidities, particularly cardiovascular disease (MM: 24% vs 5% (p<0.01); DLBCL: 25% vs 5%). Consequently, patients receiving bispecifics were less often eligible for transplant (MM: 38% vs 42%; DLBCL: 24% vs 51%). In MM, treatment goals also diverged; CAR-T was predominantly used with curative/remission intent (50% vs 25% (p<0.01)), whereas bispecifics were more often selected for palliative care (37% vs 11% (p<0.01)). Additionally, MRD testing rates in MM are higher than in DLBCL with both bispecific use (MM: 53% vs. DLBCL: 33%) (p<0.01) and CAR-T use (MM: 72% vs. DLBCL: 42%) (p<0.01). Furthermore, bispecifics were more frequently administered in offices, private clinics, or community hospitals (73% vs 67%) for MM. In DLBCL, both therapies were primarily used with curative intent (82% vs 75%, bispecifics vs CAR-T). In a notable reversal from the MM trend, bispecifics for DLBCL were more commonly given in university/teaching hospitals or comprehensive cancer centers (48% vs 26%). Like MM, MRD testing is higher with CAR-T use than with bispecifics in DLBCL patients (42% vs 33%). In multiple myeloma, bispecific antibodies have gained increasing physician satisfaction over time (mean 7.64 out of 10) and now surpass CAR-T therapies (7.29, p<0.05). The opposite pattern exists in DLBCL, where CAR-T maintains higher satisfaction (7.69) compared to bispecifics (7.05, p<0.01). However, DLBCL patients demonstrate higher engagement with their treatment compared to MM patients withDLBCL patients significantly more likely to request a specific treatment by name than MM patients (bispecific: 36% vs. 3%, p<0.01 and CAR-T: 8% vs 2%, p<0.01). In MM, sampled physicians demonstrate a higher propensity to prescribe bispecifics due to their perceived tolerability, with 29% opting for bispecifics compared to 15% for CAR-T therapies. Conversely, in the context of DLBCL, the disparity in selecting a treatment class based on tolerance is less pronounced, with 12% favoring bispecifics over 8% for CAR-T therapies. Conclusion: Data from this study reveals highly distinct patient selection paradigms for bispecifics and CAR-T therapies that differ between MM and DLBCL. CAR-T therapy is generally utilized for younger, fitter patients with curative intent, especially in MM. Bispecific antibodies serve a critical role for an older, more comorbid, and more heavily pre-treated patient population that may be ineligible for other therapeutic options. These findings underscore the complementary, rather than competing, roles of these two powerful immunotherapies in modern hematology practice.