Partial　nitritation-anammox　(PN/A)　process　is　known　as　an　energy-efficient　technology　for　wastewater　nitrogen　removal,　which　possesses　a　great　potential　to　bring　wastewater　treatment　plants　close　to　energy　neutrality　with　reduced　carbon　footprint.　To　achieve　this　goal,　various　PN/A　processes　implemented　in　a　single　reactor　configuration　(one-stage　system)　or　two　separately　dedicated　reactors　configurations　(two-stage　system)　were　explored　over　the　past　decades.　Nevertheless,　large-scale　implementation　of　these　PN/A　processes　for　low-strength　municipal　wastewater　treatment　has　a　long　way　to　go　owing　to　the　low　efficiency　and　effectiveness　in　nitrogen　removal.　In　this　work,　we　provided　a　comprehensive　analysis　of　one-stage　and　two-stage　PN/A　processes　with　a　focus　on　evaluating　their　engineering　application　potential　towards　mainstream　implementation.　The　difficulty　for　nitrite-oxidizing　bacteria　(NOB)　out-selection　was　revealed　as　the　critical　operational　challenge　to　achieve　the　desired　effluent　quality.　Additionally,　the　operational　strategies　of　low　oxygen　commonly　adopted　in　one-stage　systems　for　NOB　suppression　and　facilitating　anammox　bacteria　growth　results　in　a　low　nitrogen　removal　rate　(NRR).　Introducing　denitrification　into　anammox　system　was　found　to　be　necessary　to　improve　the　nitrogen　removal　efficiency　(NRE)　by　reducing　the　produced　nitrate　with　in-situ　utilizing　the　organics　from　wastewater　itself.　However,　this　may　lead　to　part　of　organics　oxidized　with　additional　oxygen　consumed　in　one-stage　system,　further　compromising　the　NRR.　By　applying　a　relatively　high　dissolved　oxygen　in　PN　reactor　with　residual　ammonium　control,　and　followed　by　a　granules-based　anammox　reactor　feeding　with　a　small　portion　of　raw　municipal　wastewater,　it　appeared　that　two-stage　system　could　achieve　a　good　effluent　quality　as　well　as　a　high　NRR.　In　contrast　to　the　widely　studied　one-stage　system,　this　work　provided　a　unique　perspective　that　more　effort　should　be　devoted　to　developing　a　two-stage　PN/A　process　to　evaluate　its　application　potential　of　high　efficiency　and　economic　benefits　towards　mainstream　implementation.　©　2023　Elsevier　B.V.