The β₁- and β₂-adrenergic signaling systems play different roles in the functioning of cardiac cells. Experimental data shows that the activation of β₁-adrenergic signaling system produces significant inotropic, lusitropic, and chronotropic effects in the heart, while the effects of the β₂-adrenergic signaling system is less apparent. In this paper, a comprehensive compartmentalized experimentally-based mathematical model of the combined β₁- and β₂-adrenergic signaling systems in mouse ventricular myocytes is developed to simulate the experimental findings and make testable predictions of the behavior of the cardiac cells under different physiological conditions. Simulations describe the dynamics of major signaling molecules in different subcellular compartments; kinetics and magnitudes of phosphorylation of ion channels, transporters, and Ca²⁺ handling proteins; modifications of action potential shape and duration; and [Ca²⁺]_i and [Na⁺]_i dynamics upon stimulation of β₁- and β₂-adrenergic receptors (β₁- and β₂-ARs). The model reveals physiological conditions when β₂-ARs do not produce significant physiological effects and when their effects can be measured experimentally. Simulations demonstrated that stimulation of β₂-ARs with isoproterenol caused a marked increase in the magnitude of the L-type Ca²⁺ current, [Ca²⁺]_i transient, and phosphorylation of phospholamban only upon additional application of pertussis toxin or inhibition of phosphodiesterases of type 3 and 4. The model also made testable predictions of the changes in magnitudes of [Ca²⁺]_i and [Na⁺]_i fluxes, the rate of decay of [Na⁺]_i concentration upon both combined and separate stimulation of β₁- and β₂-ARs, and the contribution of phosphorylation of PKA targets to the changes in the action potential and [Ca²⁺]_i transient.