Organic Rankine cycle (ORC) engines are suitable for heat recovery from internal combustion engines (ICE) for the purpose of secondary power generation in combined heat and power (CHP) systems. However, trade-offs must be considered between ICE and ORC engine performance in such integrated solutions. The ICE design and operational characteristics influence its own performance, along with the exhaust-gas conditions available as heat source to the ORC engine, impacting ORC design and performance, while the heat-recovery heat exchanger (ORC evaporator) will affect the ICE operation. In this paper, an integrated ICE-ORC CHP whole-system optimisation framework is presented. This differs from other efforts in that we develop and apply a fully-integrated ICE-ORC CHP optimisation framework, considering the design and operation of both the ICE and ORC engines simultaneously within the combined system, to optimise the overall system performance. A dynamic ICE model is developed and validated, along with a steady-state model of subcritical recuperative ORC engines. Both naturally aspirated and turbocharged ICEs are considered, of two different sizes/capacities. Nine substances (covering low-GWP refrigerants and hydrocarbons) are investigated as potential ORC working fluids. The integrated ICE-ORC CHP system is optimised for either maximum total power output, or minimum fuel consumption. Results highlight that by optimising the complete integrated ICE-ORC CHP system simultaneously, the total power output increases by up to 30% in comparison to a nominal system design. In the integrated CHP system, the ICE power output is slightly lower than that obtained for optimal standalone ICE application, as the exhaust-gas temperature increases to promote the bottoming ORC engine performance, whose power increases by 7%. The ORC power output achieved accounts for up to 15% of the total power generated by the integrated system, increasing the system efficiency by up to 11%. When only power optimisation is performed, the specific fuel consumption increases, highlighting that high-power output comes at the cost of higher fuel consumption. In contrast, when specific fuel consumption is used as the objective function (minimised), fuel consumption drops by up to 17%, thereby significantly reducing the operating fuel costs. This study proves that by taking a holistic approach to whole-system ICE-ORC CHP design and operation optimisation, more power can be generated efficiently, with a lower fuel consumption. The findings are relevant to ICE and ORC manufacturers, integrators and installers, since it informs component design, system integration and operation decisions.