Background/Objectives: Hematopoietic stem cell transplantation (HSCT) exposes patients to cardiovascular stress through inflammation, metabolic disturbances, and prior cardiotoxic therapies. Although overt dysfunction is uncommon early after transplantation, subclinical cardiac adaptation remains poorly defined. Methods: We evaluated early electrical and mechanical cardiac responses after HSCT using integrated electrocardiographic (ECG) and echocardiographic assessment. In this prospective cohort study, patients underwent paired pre-transplant and early post-transplant (3–6 months) ECG and comprehensive echocardiography, including tissue Doppler and speckle-tracking analyses of atrial, ventricular, and right heart function. Results: Patients were stratified into multiple myeloma (MM) and non-MM subgroups. ECG voltage increased after HSCT, particularly in MM patients, without changes in left ventricular (LV) mass, geometry, or global systolic indices, suggesting electrical–structural dissociation. Left atrial (LA) reservoir strain decreased despite stable atrial volumes. Diastolic indices showed selective modulation, including a group-time interaction in the lateral e′/a′ ratio without elevated filling pressures. Subgroup analyses suggested divergent myocardial responses, with numerical global longitudinal strain (GLS) improvement in MM patients and reduced LV deformation and right ventricular (RV) fractional area change in non-MM patients. Conclusions: Early cardiac responses after HSCT were heterogeneous and compartment-specific, supporting multiparametric imaging for detection of subclinical cardiac adaptation.