We analyze different optimization strategies for real-time energy management in building systems. We have found that exploiting building-wide multivariable interactions between CO2, humidity, pressure, occupancy, and temperature leads to significant reductions of energy intensity. Our analysis indicates that it is possible to obtain drastic energy savings compared with traditional control strategies. The exploitation of the thermal comfort zone has been found to be the most relevant factor driving energy savings. We discuss strategies to handle multiple competing objectives as well as economic functions and we analyze financial incentives provided by real-time prices and existing market designs. Numerical experiments are provided to support the claims.