The application of partial nitritation and anammox processes (PN/A) to remove nitrogen can improve the energy efficiency of wastewater treatment plants (WWTPs) as well as diminish their operational costs. However, there are still several limitations that are preventing the widespread application of PN/A processes in urban WWTPs such as: (a) the loss of performance stability of the PN/A units operated at the sludge line, when the sludge is thermally pretreated to increase biogas production; (b) the proliferation of nitrite-oxidizing bacteria (NOB) in the mainstream; and (c) the maintenance of a suitable effluent quality in the mainstream. In this work, different operational strategies to overcome these limitations were modelled and analyzed. In WWTPs whose sludge is thermically hydrolyzed, the implementation of an anerobic treatment before the PN/A unit is the best alternative, from an economic point of view, to maintain the stable performance of this unit. In order to apply the PN/A process in the mainstream, the growth of ammonia-oxidizing bacteria (AOB) should be promoted in the sludge line by supplying extra sludge to the anaerobic digesters. The AOB generated would be applied to the water line to partially oxidize ammonia, and the anammox process would then be carried out. Excess nitrate generated by anammox bacteria and/or NOB can be removed by recycling a fraction of the WWTP effluent to the biological reactor to promote its denitrification.