An engine cylinder misfire detection system is provided that detects changes in exhaust manifold pressure (EMP) fluctuations, compares the EMP fluctuations with diagnostic thresholds determined with other engine characteristic information obtained from engine sensor data, and determines whether a cylinder misfire has occurred. A method of monitoring and detecting EMP fluctuations in combination with one or more sensed engine characteristics is disclosed to determine an engine cylinder misfire in a cycle of an internal combustion engine having at least one cylinder. The actuation approaches of the present invention include one or more processes for a cylinder of an engine associated with a determination of various load variables including fresh air flow, engine type, engine data inputs, and analytical determinants.