This study investigates the economic viability of small-scale, multi-generation systems (combined heat and power (CHP), combined cooling, heating, and power (CCHP)), along with conventional heating and cooling systems combining sixteen heating/cooling energy generation systems (H/C-EGSs). The Energy Performance of Buildings Directive (EBPD) comparative framework methodology is followed. The local cost-optimal solution for an office building, in Helsinki, Finland is determined for each H/C-EGS as well as the global cost-optimum. The suggested energy efficiency measures get 144 building combinations, and alongside the H/C-EGSs, altogether 2304 cases. The results show that the global cost-optimum belongs to the ground source heat pump with free ground cooling. The investigated biomass-based CHPs are economically viable only with high overall efficiency and low power-to-heat ratio due to both low investment and operational costs. The biomass-based CCHPs do not have economic or environmental benefits over the biomass-based CHPs due to the significant increase entailed of both investment and operational costs. The fossil fuel-based CHPs with high operational costs are the worst solutions economically and environmentally. Extending the cost optimal solutions by a photovoltaic panels system yields the net zero-energy office building with minimum life-cycle costs as well.