In this work, the feasibility of nuclear processes is studied via classical thermodynamics by assessing the change in entropy, a parameter that has so far been neglected in the analysis of these reactions. The contribution of the entropy to the reaction spontaneity plays a different role in the fission and fusion reactions. In particular, in fusion reactions the temperature acts as a very powerful amplifier of the entropic term (−T ΔS) that, at the temperature of tokamaks (millions Kelvin), may significantly reduce the thermodynamic spontaneity of these processes. A new approach is followed for assessing the feasibility of the D-based reactions of interest for the magnetically confined nuclear fusion through the investigation of the effect of the temperature on both kinetics and thermodynamics. The results confirm that the deuterium–tritium reaction is the most promising fusion reaction to be realized in tokamak devices. At the temperature of 1.5 × 108 K (≈13 keV), the DT reaction exhibits a large thermodynamic spontaneity (ΔG = 16.0 MeV) and its reactivity is of the order of 10−22 m3/s, a value capable of guaranteeing the tritium burning rate needed to operate the nuclear plants under tritium self-sufficiency conditions and with a net energy production. The other results show that at the tokamaks’ temperature the two branches of the DD reaction exhibit a modest spontaneity (ΔG around −2 MeV) coupled to very low reactivity values (10−24 m3/s). The temperature rise that could be aimed to increase the reactivity is however ineffective to improve the reaction feasibility since it would augment the entropic term as well, thus shifting the ΔG towards positive values. The D3He reaction is soundly spontaneous at the tokamaks’ temperature (ΔG values of −17.2 MeV) while its kinetics is close to that of the DD reactions, which are at least two orders of magnitude lower than that of the DT reaction.